The impact of allergic disease in South Africa is a cause for concern across a wide spectrum of influence, especially to the providers of health care.  Atopy-related diseases such as asthma, childhood eczema, allergic rhinitis and urticaria have been increasing globally in prevalence over the past two to three decades.  The prevalence of atopic disease is now thought to be in the region of 25%.

The postponement of allergic disease in infancy appears to be associated with a decrease in the severity of ensuing allergic disease in adults.  It has therefore seemed rational to suggest that any methods aimed at preventing or even delaying the onset of infantile allergic symptoms should be encouraged, in spite of the considerable cost in terms of time and effort needed for the effective implementation of any prophylactic regimen.  Because of these inherent difficulties, this regimen should be reserved only for the “high-allergic-risk” infant.

A. The principles of allergy prevention

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The accurate identification or prediction of the “high-allergic-risk” newborn is an integral first step in the prevention programme.  This needs to occur before, or as soon as possible after, conception in order to allow the mother to practise adequate antenatal prophylaxis in terms of the modification of her own environment.  The human foetus is able to produce Immunoglobulin E (IgE) from the 11 th week of gestation.  It has furthermore been shown that the unborn foetus is able to mount an intra-uterine allergic response to various allergens which are presumed to have crossed the materno-fetal placental barrier.

Since atopic disease has been shown to be hereditary, the "high-allergic-risk” newborn may be identified by using the following techniques:

i. An adequate family history which focuses on the presence or absence of atopic disease in the prospective mother, her husband and her existing children. (i.e. in the first degree relatives of the new born).

ii. The cord blood total polyclonal IgE assay.

If these measures have not been performed at birth, it is possible to monitor the development of specific IgE antibodies to common ubiquitous allergens during infancy, as possible predictors for subsequent allergic diseases.  While not optimal, because of the fact that sensitisation will have already occurred, it is nevertheless of use in some situations

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B. Predictions of the

“high-allergic- risk” phenotype

 i. Identifying the high-risk Newborn

1. The atopic family history

The high-risk pregnancy may be identified by an adequate family history which focuses on the presence or absence of atopy in the prospective mother, her husband, and her existing children.  Kjellman (Ref. 1) has laid down clear probability guidelines for the risk of atopic development in offspring who have an atopic family history.  These statistics show that the family history of the unborn infant is a good predictor of allergy in its future lifetime, and that the risk of allergic disease for the unborn baby increases with increasing numbers of close relatives with allergy.  Table 1 denotes the principles of the family score assessment, recommends which newborns need the cord blood IgE in vitro test at birth, and clarifies which newborns need to embark on the preventative programme during infancy.

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2. Neonatal predictive in vitro tests

With regard to the identification of the “high-allergic-risk” newborn, the concentration of total serum IgE in newborns has been used as a predictive atopic marker in Caucasoid newborns.  These studies have suggested that white newborns in Western First World countries with raised cord blood IgE concentrations are at significant risk of developing future atopy.  These neonates are advised to adopt the preventative regimen during infancy.  Controversy currently surrounds the exact predictive cut-off threshold level for the cord blood IgE concentration, above which level the newborn is “at risk”.  Values of 0.02 kU/l, 0.5 kU/l and 0.9 kU/l have been proposed. 

Recently, there have been reports questioning the predictive value of cord blood IgE determination.  Merret et al, Hide et al and Ruiz et al (Ref. 2,3,4) have all found cord blood serum IgE an insensitive predictor for future atopic disease, primarily because of the absence of an accepted and reliable threshold cutt-off value.  Nevertheless, the report of Merret and Hide came to these conclusions using “eczema” and “wheezing” as the atopic end-points during infancy. 

Studies in Caucasian African newborns, using a combination of a broad range of well defined clinical spectra, and also objective immunological criteria (RAST test positivity during infancy) showed clear differences in the cord blood total IgE concentrations between those infants who become sensitised during infancy, and those who did not.  There was not, however, a reliable threshold cut-off level for the cord blood IgE concentrations to differentiate the high-risk newborns, although these studies were not specifically designed to do so.  A cut-off level of 0.2 kU/l in First World, Caucasian communities seems to be the most acceptable for practical usage until this issue is resolved.

Other potential cord blood atopic markers, such as anti-bovine milk-specific IgG, total eosinophil counts and platelet counts, have been suggested as additional potential atopic markers.  At present the predictive relevance of these atopic markers is being assessed.

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ii Specific preventative initiatives

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With the preceding considerations as the background rationale for the specific preventative measures advocated for the “high-allergic-risk” pregnancy and newborn, the following recommendations currently apply.

 a.  Planning the time of conception and birth

Recent evidence has indicated that babies who are born in the spring, when the pollen season is at its peak, have developed a higher incidence of pollen-related allergic disease than babies born in a season when there is a low environmental count of pollens.  It may, therefore, be a worthwhile preventative factor to plan the projected date of conception and the subsequent birth of the infant to avoid the spring pollen season.  This may be a particularly important preventative measure in those families who have a family score of 4 or more.

  b. Modification of the pregnant mother’s diet and  environment

Much controversy has surrounded the role of the mother’s diet while she is pregnant, as to the effect of transplacental passage of allergens on the possible causation of allergy in the newborn.  Swedish researchers have recently come up with new evidence to show that a mother’s diet while she is pregnant did not influence the pattern of allergic disease in her offspring but other scientists disagree.

In the past, the main principle during pregnancy was to manipulate the diet of the mother so as to prevent allergic foods from making contact with the high-allergic-risk unborn foetus.  The current recommendation is for the pregnant mother to ingest whatever balanced diet she feels is recommended for pregnancy in general, but to exclude highly allergenic foods from her diet if possible.

The other important preventative step the pregnant mother should take is to avoid inhaling cigarette smoke.  This also means the avoidance of other people’s cigarette smoke (passive smoking).  Exposure of the foetus to the effects of cigarette by the pregnant mother causes increased levels of IgE in the cord blood of the newborn, and an increased risk of allergy in infancy and childhood.

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  c. Feeding methods in the Infant

1. Milk feeds

The ideal method of feeding for the high-allergic-risk baby in the first 6 months after birth is by giving him or her the benefit of breast milk only.  The emphasis on breast milk alone for 6 months is eminently possible with a little help from the doctor, the district sister, the local clinic or from the Breast Feeding Association.  The help of a dietitian may also be needed.  They will encourage and support the nursing mother.

If the baby’s weight gain is inadequate, a milk supplement such as Nutramigen may be added.  Nutramigen is a protein hydrolysate substitute containing protein, carbohydrate and fat in the correct proportions for a growing infant, but it is potentially less allergenic than a cow’s milk formula.  Cow’s milk, in any form, must be strictly avoided in the first 6 months for the reasons stated above.

Breast feeding should be continued for as long as possible after the initial 6 months critical period.  Should breast feeding not be possible, then a hypo-allergenic milk with a low potential for causing allergy should be used until 1 year of age.

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2. Solids

Ideally, no solids should be introduced during the first 6 months of life.  After 6 months of age, the step-wise and gradual introduction of relatively non-allergenic solid foods is allowed, e.g. rice, barley, cereal, pears, veal, turkey, lamb.  Allergenic foods such as dairy products, fish, eggs and citrus fruits should be avoided in the first year of life.

The mother should be reminded that a paediatrician’s or dietitian’s advice and help may be needed in planning a non-allergic diet for the infant.  As for all healthy and growing babies, a regular check should be made on weight gain.

3. Diet and the breast-feeding mother

Allergens in foods eaten by the breast-feeding mother can be secreted in her breast milk and thereby find their way to the breast-fed baby.  While it has not been conclusively shown that the mother’s diet while breast feeding adversely affects the lactating infant in the long term, in some individual cases, it is clear that the mother’s diet can directly cause eczema and other forms of food allergy in her infant through the excretion of harmful allergens in her breast milk.  It is therefore, advisable that the breast-feeding mother should restrict her diet to exclude highly allergenic foods.

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  d. Environmental manipulation and control

Environmental allergens should be rigorously excluded from the baby’s environment.  Strict exclusion of birds and furry animals such as cats, dogs and rodent pets from the house is mandatory.  If a dog is necessary for security reasons, it should be kept outside at all times.  Cockroaches and household pests such as rats and mice should be eradicated.  House dust control measures, with frequent vacuum cleaning of bedding and the bedroom, as well as the judicious use of acaricides, should control mite exposure.  House-moisture removal or desiccation should minimise mould and mite growth.

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  e. Non-specific enhancing factors for Allergy

It is important to minimise the effect of non-specific adjuvant enhancing factors for allergy.  Parental smoking should be discouraged as a general principle.  The 3-in-1 DPT inoculation should possibly be delayed because of the adjuvant effect on IgE stimulation of the pertussis component.  Respiratory viral infections should be minimised.  In this regard, over-populated day-care centres are not recommended for high-allergic-risk infants, nor is indiscriminate kissing of the baby by well-meaning friends to be encouraged.

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  f. Allergy prevention using medication

It has been clearly shown that, by delaying the onset of early allergic conditions, the risk and severity of subsequent allergic disease can be minimised.  In this regard, researchers have recently shown that, in high allergic risk infants who already had signs of eczema, the administration of Ketotifen (Zaditen) helped to prevent the development of subsequent asthma in many instances (Ref.5).  Furthermore, in young children with chronic chest symptoms, Ketotifen usage resulted in the need for less additional medication and fewer doctor’s consultations.

It seems, therefore, that in high-allergic-risk infants and children who are already showing signs and symptoms of allergic disease (such as eczema for example) the use of Ketotifen may significantly delay the progression of the allergic process by preventing more serious allergic conditions such as asthma.

Table 1
Family Score Assessment

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References

1.Kjellman N-IM, Serum IgE and the predictive value of IgE determination In: Businco L, ed. Proceedings of International Allergy Workshop:  Advances in Paediatric Allergy.  Amsterdam:  Excerpta Medica, 1982: 69.

2.Merrett T, Burr M.  Is the determination of cord blood total IgE levels of any value in the prediction of atopic disease?  Clin Exp Allergy 1992; 22: 506.

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