Infant intervention

Breast feeding vs. cows' milk vs. other milks

There are large variations between the studies comparing the different milks, namely breast milk, soya, hypoallergenic formulae (partially or extensively hydrolysed cows' milk), and cows' milk formulae given to the infant and the development of allergy. Many of the studies have looked for effects of the type of infant milk feeding on the development of allergic respiratory or skin disease, rather than on food or immunological (skinprick/specific IgE) reactions. A number of the early studies attempting to look at the impact of the infant milk formula on the risk of developing adverse food reactions showed a marginal reduction in skin test reactions and clinical adverse reactions to cows' milk (Hamburger 1984, Host et al. 1988, Saarinen and Kajosaari 1995). However, many were not randomised or prospective in their design. The more recent studies which attempt to look at the impact on adverse food reactions are randomised (Table 10.16) and use food challenge and skinprick/specific IgE endpoints, and occasionally eczema, as markers for adverse food reactions.

Of the studies listed in Table 10.16 only one shows a reduced specific IgE and clinical reactivity to milk in the intervention group with a partially hydrolysed formula, an effect that disappeared after 6 months of age (Vandenplas et al. 1995). The one other study that did suggest a reduction in reactions to cows' milk in breast/hydrolysate-fed babies versus unmodified cows' milk using open food challenge is flawed by the intervention group having a different year of recruitment for the control (cows' milk) group (Halken et al. 1993). The other studies do not consistently support any link between the type of infant milk feed and the development of adverse food reactions if skinprick/specific IgE and food challenge criteria are applied.

A number of studies in Table 10.16 use eczema, which in the early years may be associated with food intolerance, as the endpoint. The studies consistently show a protective effect of breast milk or cows' milk based hydrolysates versus unmodified cows' milk based formula on the development of eczema in the first 12-48 months of life in an atopic population (Chandra and Hamed 1991, Mallet and Henocq 1992, Vandenplas et al. 1995, Oldaeus et al. 1997). Only one small study looking at a normal population suggests a benefit of breast milk over cows' milk in reducing the risk of eczema, but with only short-term follow-up (Lucas et al. 1990). The data do not consistently support any benefit of breast feeding over a hydrolysed formula, nor do they favour an extensively hydroysed formula over a partially hydrolysed one. Soy-based formulas confer no protective benefit, and no evidence supports the use of goat or sheep milk which immunologically cross-react with cows' milk (Miskelly et al. 1988, Chandra et al. 1989, Chandra and Hamed 1991).

In conclusion, international studies do not suggest the view that different infant formulae or prolonged breast feeding reduce the risk of IgE mediated milk or other food allergies. However, there is a consistent view from a number of studies, particularly in regard to the atopic population, that breast milk and milk hydrolysates do reduce the risk of developing eczema in early childhood, an effect that disappears after 4-5 years of age.

Introduction of solids

There are no good prospective randomised studies looking specifically at the effect of delaying the introduction of solids on the risk of adverse food reactions. Prospective, non-randomised studies from a normal population (Fergusson et al. 1990) and an atopic population (Kajosaari 1991) have shown that delayed introduction of solid foods for 4-6 months reduced the risk of eczema. The study using a normal population showed a risk of chronic/recurrent eczema 2.9 times greater in those infants fed four or more solid foods before the age of four months compared with infants receiving no solid foods before four months of age. This difference was maintained until ten years of age (Fergusson et al.

Table 10.16 Prospective, randomised trials assessing the effect of infant milk feeding on the development of adverse food reactions

Study (reference)

No and type of subjects

Infant milk

Follow-up period (yrs)

Definition of adverse food reaction


Lucas etal. 1990

75, preterm, population based

Chandra and Hamed 288, atopic population, 1991 birth cohort

Schmitz et al. 1992 256, population based, birth cohort

Mallet and Henocq 1992

Vandenplas et al. 1995

165, atopic population, birth cohort

58, atopic population, birth cohort

Breast milk vs. preterm cows' milk for 1.5 months

Whey hydrolysate vs. cows' milk vs. soya vs. breast fed > 4 months

Cows' milk vs. partially hydrolysed casein for first few days in breast-fed babies

Casein hydrolysate vs. cows' milk for 4 months

Partially hydrolysed whey vs. cows' milk for 6 months


Sp IgE/SPT to cows' milk and soya Eczema


Sp IgE to cows' milk Eczema

Sp IgE to cows' milk Eczema

Open FC

Sp IgE to cows' milk at 6 months Eczema

Reduced eczema in breastfed group up to 18 months

No difference in sp IgE/SPTs Increased eczema in cows' milk and soya groups

No difference

No difference in sp IgE Reduced eczema up to 4y

At 6 months 33% of control group had intolerance to cows' milk vs. 4% in intervention group (p=0.006). No difference at 1y. Reduced cows' milk IgE in intervention group at 6 months

Reduced eczema in intervention group up to 1y

Oldaeus et al. 1997

155, atopic population, birth cohort

Partially hydrolysed (PH) vs. extensively hydrolysed (EH) vs. cows' milk (CM) vs. breast fed (BF) for 9 months

De Jong et al. 1998

1533, population based, birth cohort

Cows' milk vs. protein-free formula for first 3 days in breast-fed babies

Open or DBPC food challenges in 20% SPT & sp IgE to egg & cows' milk Eczema




No difference in positive FC Increased SPT to egg in PH group at 9 months but not at 18 months

Increased eczema in CM and PH up to 9 months and in CM at 18 months, compared with BF & EH groups

No difference

1990). In the study of an atopic population, eczema and a history of food allergy were reduced at the age of one year in the group fed solids after six months of age compared with those with solids introduced at three months. No food challenges or skinprick/IgE testing were performed in the first year, but at five years there was no difference between skin testing to fish, milk and wheat, history of food allergy and eczema between the two groups (Kajosaari 1991). A randomised, population-based study in Finland showed no difference in the cumulative incidence of fish and citrus allergy at three years old between children with fish introduced early or late (after one year old) into the diet, although the children with earlier introduction reacted earlier in life (Saarinen and Kajosaari 1980). Similar observations have been reported with coeliac disease. The later introduction of gluten into the infant diet has altered the age of onset and type of clinical presentation of coeliac disease in countries such as the UK and Scandanavia, but does not seem ultimately to stop the development of the disease, a view supported by the increase in serological population screening studies (Logan 1992, Ascher 1996, Hallert 1998).

Various guidelines exist in the UK recommending delayed introduction of solids in infants at increased risk of atopy, and in the same at-risk group delaying the ingestion of peanut products until after three years of age (Committee on Toxicity of Chemicals in Food 1998). On the basis of the studies presented, these guidelines do not appear to be evidence-based. Furthermore, the observation that 88% of egg reactions and 80% of peanut reactions occur after the first known exposure (Ford and Taylor 1982, Hourihane and Kilburn 1997) suggests that allergen avoidance is not straightforward and sensitisation may occur earlier in life and by other means, such as food contamination or inhaled sensitisation (Witteman 1995).

In conclusion, the evidence to date suggests that delaying the introduction of a solid food will perhaps postpone rather than prevent the development of clinical food allergy. There are no data suggesting that immunological (skin test or specific IgE) reactivity is affected. Thus, at the age of five years no difference in sensitisation to foods between those with solids introduced early or late into the diet can be found (Kajosaari 1991). These observations are probably not surprising as a delay in the age at which clinical reactivity develops may simply reflect the timing of the food being introduced into the diet, thereby giving the individual the first opportunity to clinically react to the food. Although there is some evidence that delaying the introduction of solids to 4-6 months reduces the risk of eczema in the medium term, the data come from non-randomised studies, and thus have to be interpreted with caution.

Combined maternal and infant measures

Two of the best trials in the field of dietary avoidance involve combined maternal and infant interventions (Zeiger and Heller 1995, Hide et al. 1996). Both are prospective and randomised with assessments by physicians blinded to the randomisation group in an atopic population. Both used skin test/specific IgE and food challenge criteria as endpoints for adverse food reactions, as well as other

Table 10.17 Prospective, randomised trials assessing the effect of mixed maternal and infant dietary measures on the development of adverse food reactions

Study (reference)

No. and type of subjects

Maternal and infant diet

Follow-up period (yrs)

Definition of AFR


Zeiger et al. 1989

288, atopic population,

Maternal egg, cows'


DBPCFC (50% of

Reduced food

Zeiger and Heller 1995

birth cohort,

milk and peanut


intolerance at 1y and

randomised, physician

avoidance in 3rd

Sp IgE/SPT to cows'

reduced cows' milk IgE/


trimester and lactation + infant breast or casein hydrolysate (6 months), cows' milk and solids delayed > 6 months (later for some solids) vs. American Academy of Pediatrics guidelines

milk, egg, wheat, corn, soy, peanut, cod, chicken/beef

SPT at 1y and 2y in intervention group Reduced eczema at 1y in intervention group

Arshad et al. 1992

120, atopic population,

Maternal egg, cows'


Open challenge

Differences in

Hide etal. 1996

birth cohort,

milk, fish and nuts

SPT to cows' milk,

prevalence of cows'

randomised, physician

exclusion during

egg, wheat, fish,

milk/egg intolerance and


lactation + infant breast +/— soy hydrolysate, solids delayed >11 months vs. no restrictions

peanut Eczema

food SPTs did not reach statistical significance Reduced eczema until 4y in intervention group

atopic diseases including eczema (Table 10.17). One study involved maternal dietary restriction in pregnancy and lactation, infant breast or casein hydrolysate feeding for six months, and delayed introduction of solids until at least six months into the infant diet (Zeiger and Heller 1995). There was a reduction in adverse food reactions in the intervention group at one year of age using a combination of clinical history and DBPCFC for diagnosis. These differences were almost entirely due to cows' milk allergy. The effect had disappeared by two years of age. The intervention group also showed a significant reduction in cows' milk specific IgE and cows' milk skinprick test at one and two years of age, but not thereafter. There were equal numbers sensitised to peanut at all ages including seven years when this was the commonest positive food allergen. Eczema was reduced at one year in the intervention group but not thereafter. The second study from the Isle of Wight cohort (Hide et al. 1996) involved maternal food avoidance during breast feeding and infant cows' milk avoidance until nine months with breast or soya hydrolysate used until then and egg introduced as the first solid at 11 months. There were reduced numbers of subjects with positive food challenges and food skin tests, mostly at one year old but never reaching statistical significance. Eczema was reduced until the four-year follow-up.

The conclusions from combined maternal and infant dietary exclusions are of a reduction in cows' milk allergy until 1-2 years of age, and a reduction in eczema in the first 1-4 years of life. As the natural history of cows' milk allergy is one of natural resolution by the age of two years in the vast majority, it is not surprising that the effect of dietary avoidance on food allergy disappears by two years of age. These studies on combined exclusion diets show no long-term benefit in preventing egg, peanut and other persistent food allergies.

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