1. Prediction
of Atopy
Prediction
of atopic disorders is an important step and should be carried out by examining
both genetic factors and neonatal conditions.
It
has been known for centuries that heredity plays an important role in the
development of atopy. A child with a negative family history still has about a
5-15% risk of developing atopy. However, children with a parental history of
atopic disease are at higher risk for the development of atopic symptoms. It
has been found that if one parent is affected, the chances of an offspring
being affected vary between 20 and 4O%. If both parents are affected the figure
increases up to 40-60%, and 50-80% if both show the same allergic
manifestations. The risk of atopy in children who have an allergic sibling
ranges between 25 and 35% [3,10].
The importance of
genetic factors is also demonstrated by other data:
(I) children with
positive family history for atopy develop allergic symptoms earlier than those with
a negative family history [11],
(II) The higher the
incidence the higher the number of affected subjects in the same family [3].
Notable
differences exist in the so-called predisposition to atopic diseases, and
further study appears to be necessary to better delineate the role played by
genetic factors in the development of such disorders.
In
many allergic patients total serum IgE levels are found to be elevated, and it
has been shown that a high total serum IgE level in infants is often associated
with the subsequent development of atopic symptoms. Therefore, it was proposed
that the measurement of IgE by PRIST testing in infants or at birth would have
a predictive value in the atopy development. Several investigators have
demonstrated that the risk of developing atopic diseases was very high when the
cord IgE level was above 0.5 IU/ml [5,8,9,12].
Our
data shows that a newborn can be considered at risk for atopy when the cord IgE
level is above 0.8 IU/ml [5]. We have also shown
that neonates of non atopic parents (0.032 + 0.87 IU/ml in the not atopic vs.
O.295+5.12 IU/ml in the atopic newborns, p<0.005) [5].
Recent prospective studies have shown that the most accurate predictive results
are obtained when family history and cord IgE levels are evaluated together [9,12].
The
notion that a neonate is at risk either by familial history or because of high
total IgE levels or from both causes may help it to better handle the
difficulties usually associated with a prevention program. Recent personal data
obtained from a series of preterm babies of different gestational ages failed
to show any significant differences in total IgE levels according to
gestational age [13], thus suggesting that IgE synthesis
is not increased during the last months of gestation.
2. Environmental
Factors Influencing the Development of Atopic Diseases in Children
It
has been long known that a series of prenatal, neonatal and environmental
factors such as season birth, home exposure to pets and tobacco smoke, viral
infections, and dietary factors can be important in the phenotypic expression
of atopy.
2.1. Prenatal Factors
Several
studies have suggested that infections during pregnancy and food or drugs
administered to pregnant women are likely to lead to an increased risk of
developing atopic disease in babies. It has been recently reported that the IgE
concentration was higher in cord blood if the pregnant mothers had been
administered progesterone. However, these elevated levels were not associated
with an increased development of atopic disease in the infants, nor were
newborn IgM levels related to subsequent allergies [14].
Can
a baby be born allergic? Although the research in this field is scarce, some
experimental and clinical observations have shown that the sensitization can
occur during fetal life. As early as 1928, Ratner demonstrated intrauterine
sensitization to CM proteins in Guinea pigs, and speculated on analogous
sensitization in humans [15]. Subsequently, it
was found that IgE synthesis occur in utero as early as the 11th week of
gestation [16]. It was also demonstrated that
the fetus is capable of producing specific IgE antibodies to food allergens
that were ingested by the mother during pregnancy. Antibodies to CM and soybean
proteins have been detected in both the amniotic fluid and cord blood [5,17]. Since the mothers had no antibodies to these
allergens, it follows that the antibodies had been synthesized by the fetus. It
was therefore recommended to atopic women not to ingest, during pregnancy,
excessive amounts of offending foods such as eggs and CM [18,19]. Very recently a randomized study performed in
Sweden on a large population of pregnant women showed that a strict CM and egg
free diet during the last three months of pregnancy had no effect on the development
of atopy in the babies [19,20].
Light
and Worley pointed out that a history of maternal asthma, symptomatic during
pregnancy, is associated with an increased incidence of respiratory disease
and/or jaundice in newborns [21].
Another
factor in prenatal life influencing the development of atopy is the
concentration of serum IgE in the mother's blood. Michel et al found that the
more allergic the mothers, the higher the IgE concentration in the cord blood
of their newborn infants [22]. If a mother had a
serum-IgE level of more than 100 IU/ml, the serum IgE level of her newborn's cord
blood was significantly higher than that of newborns whose mothers' serum IgE
levels were less than 100 IU/ml. Conversely, Michel et al found that the IgE
levels of the infants' fathers did not appear to influence the newborn's cord
blood IgE level [22].
The
season of birth also seems to be a predisposing factor in atopy sensitization,
as first demonstrated by Soot hill et al [23] who
showed that the risk of developing a mite allergy was dependent upon the month
of birth. Subsequently a significantly higher incidence of sensitization to
pollens in children’s born in the March-May period and to mites in children
born in the September-October period has been shown by several investigators.
However, other studies have failed to confirm the above results [24].
We
have examined 2532 children aged 1-14 years, all born in the Rome province. We
showed that a significantly high proportion of children born during the
June-September period had a Dermatophagoides pteronyssinus allergy (p<0.005
), while those born during the March-May period had a grass-pollen sensitivity
( p<<0.005 ), in the Rome province for the same age period of the
children examined [24].
2.2. Perinatal
Factors
Certain
features of a child's perinatal history may significantly affect his chances of
developing bronchial asthma. Accordingly a group of psychologists at the New
York Hospital studied three groups of children to verify this hypothesis.
The
first group consisted of 30 children with bronchial asthma seen for treatment
in the Pediatric Allergy Clinic of the New York Lying-In Hospital. Each of the
other two groups consisted of children without asthma selected from the birth
records of the above hospital. They were matched with the asthmatic group by
randomly selecting two babies from the same obstetrical unit. A greater
frequency of neonatal complications was found among the asthmatic children.
These included complications from either the mother or the baby in the
perinatal period [25]. Therefore, a stressful
birth significantly increases the chances of a child subsequently developing
bronchial asthma.
2.3. Early Surgery
In
early infancy, factors other than diet seem to "turn on" allergic
diathesis. A study was carried out in order to follow-up the clinical
impression of some pediatric allergists that early surgery might increase the
risk of developing asthma or hay fever.
In
the first part of the study, 115 children who had been operated on pyloric stenos
is were followed-up and found to have had an above-average prevalence of allergic
disease. Of those who had undergone such an operation, 20% developed bronchial
asthma, 21% developed hay fever and 36% developed one or both of these
conditions [26].
These
figures were much higher than those found in household interviews in the Rochester
Child Health Study investigation of a random sample of children 0-17 years of
age in Monroe Country, USA. The study showed that 3.4% of the random sample of
Rochester children had had asthma, 8.5% had had hay fever, and 10.6% had had
one or both of these conditions [27]. In the
second part of the study, Johns tone et al reported on 47 boys who had a hernia
repair and who were followed. They showed similar results. Of those who had
undergone a herniorrhaphy in their first year of life, 34% developed asthma,
21% developed hay fever and 55% developed either one or the other [26].
In
the third part of the study, 202 children from the Rochester Child Health
Study, whose parents had reported that they had had asthma or hay fever, were
investigated for evidence of early hospitalizations or surgery. Their parents
reported significantly more hospitalizations. For the boys less than two years
of age there were significantly more operations necessitating general
anesthesia than for non-asthmatic children of the same age from the same random
population group [26].
2.4. Environmental Factors
Another
factor influencing the onset of asthma in early infancy is home exposure to
many potent allergens such as mites, furred animal danders and pollens. Pets
carry pollen and dust on their fur. When it is hot, most pets drool saliva
since they do not sweat. This highly allergenic saliva dries and becomes an
important part of what we call "house dust" in the home [28]. House dust mite appears to be the most common
offending allergen in asthma, and early exposure to this allergen is associated
with a significant increase of the risk of asthma at the age of 11 [29]. Sporik et al concluded "we believe that
increased exposure to dust mites and other indoor allergen may be a factor
contributing to the recent increases in the morbidity and mortality associated
with asthma" [29]. Previous studies have
shown that early exposure to pets significantly influence the development of
respiratory allergy to animal dander’s [30].
Morrison-Smith
reported that atopy is less common in "developing" than in
"developed" countries [31]. In a study
of immigrants to Great Britain, he confirmed the lower incidence of bronchial
asthma in children of African origin who were born outside Britain. Offspring
of parents of African origin who were born in England, however, had at least as
high a prevalence of atopic disease as non-African children. This suggests that
the difference in the prevalence of asthma in African children was environmental
rather than purely genetic [31].
Very
recently we have shown that the prevalence of AD was significantly higher in
Somali children living in Rome, in comparison with controls living in Somalia (p<0.001)
and the age of weaning was significantly lower in Somali children living in
Rome. This data again indicates that environmental factors may influence even
the onset of AD [32].
2.5. Infections
As
mentioned earlier, viral infections frequently trigger asthmatic attacks in
children. During the last few years many studies have reported that several of these
viruses, including Respiratory Syncytial Virus (RSV), par influenza (types
1-3), corona virus, adenovirus, and cytomegalovirus may contribute to the
development of allergic sensitization in the predisposed children. In children
of atopic parents, the allergic sensitization accompanied by IgE synthesis
manifested itself after viral upper respiratory infections, in coincidence with
the specific antibody response to the virus. Increased levels of IgE antibodies
have been shown in various viral infections [33,34].
Previous
studies have indicated that RSV-specific IgE antibodies are more persistently present
and that high RSV-IgE titers are associated with increased concentrations of
histamine in patients affected by RSV infections [35,36].
In addition, RSV and par influenza virus have the capacity to induce an
IgE-specific antibody response in the
Airway,
the presence and quantity of virus-specific IgE possibly being specifically
related to the severity of symptoms [37].
In
recent studies, BALB/c mice were infected intranasal with RSV and then exposed either
to ragweed or ovalbumin. The results suggested that RSV infection can enhance
the development of sensitization and the magnitude of antibody responses to
other inhaled allergens found concomitantly in the respiratory tract during
acute infection [38,39].
There
are several mechanisms by which viral infections enhance the antibody-specific
responses to concomitantly inhaled allergens, thus favoring the development of
an atopic disease. There could be alterations in the uptake and/or processing
of mucosally introduced allergens during virus-induced inflammatory damage or
preferential depression of IgE-specific T-suppressor cells, resulting in
increased IgE production. There also could be enhancement of the IgE-mediated
histamine release associated with interferon production from the leukocytes of
ragweed-allergic patients after viral infection, thereby altering vascular
permeability; and possibly, the result Beta-adrenergic blockade would
preferentially stimulate IgE antibody formation. Moreover, viruses produce
soluble factors that are chemotactic for basophils and that enhance histamine
release from basophils and mast cells [40].
2.6. Passive Smoking
Among
the environmental factors favoring the development of atopic disease, cigarette
smoke plays a primary role. Evidence is steadily accumulating that there is an
important relationship between parental smoking habits and atopic symptoms in
children.
It
has been observed that atopic symptoms start earlier in the nonsmoking children
of parents who smoke [11]. Moreover, immunologic
studies corroborate these findings. Reports of higher IgE levels in adult
smokers [41] and in infants of smoking atopic
parents [42] support the view that the
immunologic abnormalities may be relevant. The issue of whether smoking acts by
irritating the respiratory mucosa [43], which
facilitates both the penetration of antigens and the spread of infection, or by
a direct action on the immune system has yet to be resolved. Not only is
tobacco smoke an irritant, but an increasing body of evidence also indicates that
it predisposes to an increased susceptibility to respiratory viral infections.
This
fits with recent data showing that adult smokers contract influenza more
frequently. Studies have also shown a higher prevalence of recurrent
respiratory infections in children of smoking parents [43-45].
Since these affections are asthmogenic, a vicious circle is started, especially
in the winter months in which a greater viral transmission is facilitated:
parents' smoking ---> viral respiratory infections ---> asthma in the
child. As a result, only a drastic inhibition of smoking can interrupt this
cycle.
All
these results concur to stress the importance of the environmental controls.
Thus, there are grounds to forbid smoking not only in the allergic child's home,
but also in the house of any child at risk for development of allergic disease.
In addition, parents should not expose their children to passive smoking in
other confined spaces, such as the family car.
2.7. Allergy Prevention
The
possibility of preventing atopic diseases in high risk babies has been
confirmed by several groups of investigators and we point out that in order to
prevent atopic diseases in high risk babies they should be subjected not only
to dietary measures, but also to environmental measures Our prevention program
includes 1) environmental and 2) dietary manipulations such as follows:
1)
Exclusive breast-feeding for the first six months of life; total avoidance of
cow's milk, dairy products and eggs for the nursing mothers; selected weaning
after the 6th month of life; cow's milk and dairy products gradually introduced
after the 6th month and gluten shortly afterwards,
2)
No smoking in the house; environmental controls for the elimination of
house-dust mite; no pets in the house; day-care center attendance delayed to
after the 3th year of life.
2.8. Dietary Measures during Pregnancy
As
previously reported, several studies have suggested that antennal sensitization
to food antigens may occur, however this phenomenon is quite rare. Antennal
sensitization to different food antigens may be explained not only by the
transfer of nutrients via the placenta, but also by the transfer of
anti-idiotypic antibodies from the mother to the fetus.
In
order to reduce the risk of antennal sensitization, different approaches have
been suggested, aimed at modifying the mothers' diet during pregnancy. It has
been shown that the complete exclusion of milk and dairy products, eggs, fish,
beef and peanuts during the pregnancy is associated with a reduced prevalence
of AD and also a significant reduction in the severity score of the skin
lesions [46]. However, two randomized studies
failed to confirm the protective effect of dietary measures during pregnancy [19,20]. We would like to emphasize that in these
studies the dietary measures were advised only in the last trimester of
gestation and the mothers were encouraged to drink a casein hydrolyzed formula
(Nutramigen) during the dietary restriction period. We can hypothesize that the
short period of dietary restriction and the use of this formula may have
influenced the negative results (see section on hydrolysate formulas).
2.9. Prolonged Breast Feeding
The
preventive effect of breast-feeding on allergy development in high-risk infants
has been shown in several prospective studies [6, 7,
47-49]. High risk babies should be exclusively breast-fed for the first
six months of life, since human milk provides the infant not only with
homologous proteins which are non-allergenic but also with a number of immunological
factors which can prevent the absorption of macromolecules. Therefore, the
preventive effect might be antigen non-specific.
3. Dietary
measures during lactation
About
70 years ago American pediatricians documented that AD in exclusively breast-fed
infants could be related to foods ingested by their mothers, and that the
eczema cleared up when the mothers avoided the offending food(s). In addition,
it was shown that exclusively breast-fed babies with AD had positive skin tests
to foods never previously ingested. It was thus suggested that food antigens
ingested by the mothers might pass into the breast milk, thus sensitizing the
babies. This passage was first demonstrated by Stuart [50]
who found that egg-whites are present in breast-milk up to a dilution of 10.
The complete exclusion of CM, eggs, fish and peanuts during breast feeding (six
months) significantly reduced the prevalence of AD [46].
A prospective randomized study [51] demonstrated
that the avoidance of CM, eggs and fish during the first three months of
lactation was associated with a statistically significant reduction in the
prevalence of AD at the age of three and six months and a significantly lower
cumulative prevalence of atopic disease at four years of age.
We
have investigated the sensitizing effect via breast milk of a
partially-hydrolyzed (whey proteins) hypoallergenic formula. The formula was
given to 39 nursing "high risk" mothers (400 ml daily) during the
lactation period (six months) [52]. Another
group of 39 nursing "high risk" mothers, who consumed 400 ml of CM
daily, served as control. There was no significant difference in the cumulative
incidence of atopic diseases in the babies at one year of age according to the
mothers' diet. However, the prevalence of babies at 6 and 12 months with
specific IgE antibodies against the whey protein and with total IgE antibody
levels more than 2 SD from the normal values for age were significantly higher
( p = 0.02 ) in the group of babies whose mothers
received the hypoallergenic formula. This preliminary study showed that a
partially hydrolysate formula not only still contains peptides which are able
to sensitize high-risk babies via breast milk, but it seems even more
sensitizing than CM [52].
Thus,
it seems evident from the results of these studies that it is mandatory to
avoid allergenic foods such as CM, eggs, fish and peanuts throughout the
breast-feeding period in order to prevent sensitization via breast milk. In
addition, it seems from our preliminary data that CM protein hydrolysate
formulas, when given to nursing mothers,
may
also sensitize the babies. We have shown in a multicenter study which was
comprised 2.291 babies from several Italian maternity hospitals, that babies
fed breast and/or soy-milk, and whose parents strictly followed the above shown
environmental measures, had at one year of age a lower prevalence of atopic
diseases (5%) in comparison with bottle-fed babies (13%). In addition,
preventive measures were able to significantly postpone the onset and reduce
the prevalence of allergy [53]. The results of
this multicenter study confirm our previous studies which have shown that the
prevalence of atopic diseases was significantly lower at age four years in
children whose parents followed the prevention program [5-7,48].
3.1. Soy-protein formulas
Since
1929 soy protein formulas have been used for feeding infants with CMA. They are
well accepted by most infants, and their nutritional adequacy is comparable to
that of CM formulas. As such, studies were performed on infants fed a soy
formula exclusively during the first six months of life. They revealed no
immunologic abnormalities or increase in infection morbidity [54]. Regarding the composition of soy protein
formulas, they contain purified soy protein, fat is a mixture of vegetable
oils, and carbohydrates are represented by maltodextrines, corn-starch or saccharine.
Supplements of the daily recommended vitamin requirements, including vitamin D,
are added so that problems, similar to those found in premature infants, do not
arise [Review in 55]. More recently, carnitine
has been added to some soy formulas in the same amount as that found in human
milk to supplement the limited quantities stored by infants.
Carnitine,
a nitrogen quaternary base present in meat and CM, is synthesized by the body
from lysine and methionine. It allows the oxidation of long-chain fatty acids
so that they can be transferred from the cytoplasm into the mitochondria, where
they undergo Beta-oxidation, producing energy. Infants cannot synthesize
adequate quantities of carnitine from lysine and methionine because they lack
the enzymes necessary for the biosynthesis. As a consequence carnitine
deficiencies have been reported in infants fed soy formulas without added
carnitine. They are recognized by subclinical or clinical manifestations
resulting from the deficiency of the long-chain fatty acid utilization [55].
Soy
protein formulas are used for different conditions including CMA, CM protein intolerance,
lactose and galactose intolerance and in the management of infants with severe
gastroenteritis. The use of such formulas for the prevention of atopy is rather
controversial. Some studies have shown that soy formulas or breast-feeding
supplemented with soy formula for the first six months of life significantly
reduce the prevalence of atopic diseases [56,57].
In our studies, using a soy protein formula when breast-milk was not available,
we did not see an increased prevalence of soy sensitization [6,7,48,58].
However, other studies failed to show any preventive effect of soy
formulas (59, 60). These contradictory results may be explained by different
factors. The number of babies studied by Kjellman and Johansson [59] was very low, being only 23 subjects in the
study. The babies studied by Chandra et al seemed to belong to a very select
atopic-prone study group, with specific IgE and total cord blood IgE levels
which were unusually high [60].
There
is no doubt that soy proteins can induce sensitization and different allergic
manifestations. However, during the last decade soy allergen city has been
frequently emphasized in the literature, without providing data on the true
prevalence of soy allergy in different allergic diseases. Sampson has found
that only 5% of 204 patients with AD showed soy sensitivity has demonstrated by
double-blind placebo controlled challenge tests [61].
We have also confirmed this demonstrating that only 4% of 143 children with AD
showed positive challenge tests to soy [62]. In
addition, we reported a study of 21 infants with AD due to CM hypersensitivity,
where a soy-protein formula was substituted in place of CM. Twenty of these
infants showed improved skin lesions with the soy-protein formula [63].
Soy
formulas are often poorly tolerated by infants with chronic diarrhea. Infact,
intolerance to soy proteins can be a cause of chronic diarrhea often coexisting
with CM intolerance. Some investigators consider soy intolerance to be caused
by sensitivity to soy protein. However, neither a demonstration of soy
protein-sensitivity nor the mechanisms of this intolerance have been claritied.
It has been shown that a soy formula with lactose was useful for feeding
infants with chronic diarrhea and secondary multiple protein intolerance,
including CM and soy proteins [Review in 55].
In
conclusion soy formulas are nutritionally adequate and are well accepted by
many infants. Many foods such as cakes, biscuits, ice cream, desserts and
beverages can be made with soy protein formulas, thus offering children with
CMA a varied diet. Although soy proteins can be sensitizing, they are less
allergenic than CM proteins.
3.2. Hydrolysate Formulas
Hydrolyzed
formulas have been developed with the aim of decreasing or eliminating the allergen
city of CM proteins. The use of these formulas is based on the premise that
pre-digested protein, when fed as amino acids and peptides, provides nutrients
in a non-antigenic form. Thus, protein hydrolysate formulas have been
classified as "hypoallergenic".
These
formulas are processed using two main technologies: heat denaturation and
enzymatic hydrolysis to reduce the molecular weight of the peptides. The heat treatment
alters the conformational epitopes, while the enzymatic hydrolysis affects the
sequential determinants. These different technical procedures are necessary for
obtaining an acceptable palatability. However, with the reduction of the
antigenicity (peptides with very low MW) there is an associated reduction of
the palatability. The allergen city of these formulas is dependent on several
factors such as the degree of digestion, the post-hydrolysis and the protein
source itself. Extensively hydrolysate formulas are considered the most
hypoallergenic, whereas partly hydrolysate formulas are considered less
hypoallergenic and even dangerous to children with CMA [64,65].
The MW profiles of protein hydrolysates are an index of the extent of
hydrolysis According to the protein source there are three types of hydrolysate
formulas: bovine casein (Alimentum, Nutramigen, Pregestimil), bovine-whey
(Alfa-Rè, Prophylac), and soy and bovine-collagen (Pregomin). In addition, a
bovine-whey partly hydrolysate formula with lactose has been developed (Beba
HA, which is called HA in Italy and Good Start HA in US).
More
recently, a partially casein and whey-protein hydrolysate formula (Aptamil HA)
has also been developed. This product seems to be more adequate nutritionally because
it constats of 50% casein and 50% whey-protein. However, due to the less
extensive hydrolysis, this formula should be given only for prevention and not
for treatment of infants with CMA. All these formulas are supplemented with
vegetable lipids. Alfa-Rè, Alimentum and Pregestimil also contain medium-chain
triglycerides. All hydrolysate formulas, excepted Beba HA, are lactose free,
and all contain small amounts of carnitine. They are rather unpalatable
(excepted Good Start) and for this reason the compliance is poor.
Because
hydrolysate formulas are nutritionally adequate, infants generally gain weight
until they refuse the formula because of its bad taste. However, caution should
be taken when these formulas are given for prolonged periods because no data is
available on nutritional assessment of infants fed exclusively with such
formulas for several months. The only data available is from studies which have
shown animal models that hydrolysate formulas do not elicit an IgG response or
a cutaneous passive anaphylaxis. In addition, infants fed casein hydrolysates
during the first three months of life do not show IgG antibodies to the
hydrolysate formula. This data strongly suggests that these formulas are not
antigenic. However, they do contain peptides of MW greater than 2.500, which
may elicit an IgE response in predisposed infants [65].
We
initially reported [66] 5 cases of infants, aged
3-8 months (median 5 months) with an IgE-mediated CMA, who experienced
anaphylactic reactions when first fed a small amount of a whey hydrolysate
(Alfa-Rè). They all demonstrated positive skin test and RAST to both CM
proteins and Alfa-Rè. Subsequently, these infants were all successfully fed a
soy-protein formula without further consequences. This data showed that
whey-hydrolysate formulas can trigger severe anaphylactic reactions in children
with an IgE-mediated CMA [66]. Later, other cases
of anaphylactic reactions were reported in infants with IgE-mediated CMA fed
hydrolysate formulas [67-69]. Confirmation of
this is by a recent study which demonstrated residual casein epitopes in all
the hypoallergenic formulas tested: Alfa-Rè, Pregomin, and Beba HA [65]. The above data strongly supports other studies [64] which showed that antibodies raised against a CM
formula recognized epitopes displayed by peptides of other hydrolysate
formulas: Pregomin, Alfa-Rè, Nutramigen, and Pregestimil. It was also shown
that hydrolysate formulas when injected into experimental animals induced
cell-mediated immunity and that cross-reactivity exists also between IgE
antibodies to CM and peptides of hydrolysate formulas, in this limb of the
immune response. Hydrolysate formulas
Contain
protein fractions which result in a specific IgE binding after incubation with
serum samples from patients allergic to CM [65].
In
conclusion, although the proteins of hydrolysate formulas have been processed
by heat and enzymatic hydrolysis and therefore contain peptides of lower MW
than the native protein source, the peptides still have allergenic capacity and
can be recognized by the cell-bound IgE antibodies of a child allergic to CM.
As shown by an elegant study, nine of fifteen children sensitive to CM and with
a positive histamine release from mixed leukocytes also had a positive
histamine release to at least one of five tested hypoallergenic formulas [70].
According
to recent studies, extensively casein hydrolysate formulas are safer [71,72]. Generally, CM hydrolysate formulas are well
tolerated by infants with gastrointestinal symptoms caused by CM intolerance
and who do not have IgE antibodies to CM proteins.
Several
groups of investigators have used these formulas (Nutramigen or HA) as breast
milk substitute in high risk babies and although these studies have a short
follow-up, the results seems to be very encouraging [73-75].
A recent issue of the Committee on Nutrition of the American Academy of
Pediatrics states that no published, well controlled, double-blind studies
exist to support the use of whey hydrolysates either for prophylaxis or
treatment of infants with CM hypersensitivity. Limited clinical experience
suggests that a whey hydrolysate formula may be an acceptable alternative to CM
and soy protein formulas for infants intolerant, but not allergic, to CM [76]. We conclude that partly hydrolysate formulas and
whey hydrolysate formulas should not be used in infants with IgE-mediated CMA.
Further studies are needed to investigate the nutritional adequacy of hydrolysate
formulas in babies fed exclusively such formulas for several months.
3.3. Weaning
Another
important dietary preventive measure is selected weaning after the 6th month of
life. This has been shown to be a useful measure for atopy prevention [77]. However, weaning is potentially dangerous for
the high-risk baby. Special care should be addressed when new foods are
introduced into these infants' diet and offending foods such as eggs, fish, and
peanuts should be further postponed.
4. Conclusions
According
to previous and recent studies, prevention of atopic diseases in predisposed
newborn babies seems to be worthwhile. Environmental and dietary manipulations
should be addressed to "high-risk babies" in order to avoid, or
postpone the risk of sensitization, or to mitigate the clinical course of the
atopic disease once established.