Original Paper
Bio! Neonate 1992;62:10-14
Serum IgE Concentrations in the IMeonatal Period
Division of Neonatology, University of Siena, and University of Napoli, Italy
Abstract
Key Words Allergy IgE Hypoallergenic formula
The aim of the present study was to evaluate the IgE-mediated response as a predictable index of immunosensitization to dif ferent types of feeding (breast milk, adapted formula, soya for mula and serum protein hydrolyzate formula) in the first days of life. The study population included 231 newborns (128 males and 103 females). There was a family history of atopy (at least 1 parent with an atopic disease) in 116 subjects at risk for allergy. 115 newborns were without any family history of atopy. The results showed significantly higher total IgE levels on the 4th day than in cord serum in the whole group of new borns. The same result was obtained comparing subjects at risk and controls separately. No significant difference was detectable between serum IgE levels in the cord blood of the four groups. Conversely, a significant increase in IgE levels between cord and 4th day blood in soya-fed and adaptedformula-fed babies was noticed. This increase did not occur in neonates fed breast milk and serum protein hydrolyzate.
Introduction
Adverse reactions to foods are common during childhood and are closely related to the development of atopic disease [1,2]. Ac cording to the criteria utilized, the incidence of allergy is reported from 3 to almost 100% in the whole population [3] and from 26 to 30% in the pediatric population [3-6], These diseases are one of the major chronic illnesses
in developed countries and have a large eco nomic impact [7, 8]. They are multifactorial diseases based on genetic predetermination [1,9]. The first months of life are very impor tant for the development of the atopic pheno type [10, 11]. For all these reasons, the early detection of newborns at risk for allergy is of fundamental importance in the prevention of these diseases.
Dr. Giuseppe Buonocore, MD Division o f Neonatology University of Siena Via P. Mascagni, 46 1-53100 Siena (Italy)
© 1992 S. Karger AG. Basel 0006-3126/92/ 0621-0010S2.75/0
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G. Buonocore3 S. Zania B. Tomasinia V. Tripodib S. Granob R. Braccia
Materials and Methods In this paper, wc report the data of a prospective, randomized, double-blind, control study in which IgE serum levels in four groups of babies were compared. The groups were fed with breast milk, adapted formu la, soya formula and serum protein hydrolyzatc for mula (Nidina H.A.-Nestle). respectively. The study population included 231 newborns (128 males and 103 females). There was a family history of atopy (at least 1 parent with an atopic disease) in 116 subjects at risk for allergy. 115 newborns were without any family his tory of atopy (table 1). None of the neonates showed any evident clinical pathology. Gestational age was 40 ± 2 weeks. Body weight was 3,300 ± 500 g. Feeding started with 5% dextrose solution at 3-6 h of life and continued every 3-4 h until the rise of the mothers’ milk. Infants were formula fed in cases of refusal or inability to breast feed. All babies were studied for the first 4-5 days of life. This short period of follow-up was chosen because it permitted strict separation into four different types of feeding and avoidance of other food
Table 2. Serum IgE levels (IU/ml; means ± S D ) in cord and 4th day blood of newborns
allergens. All babies remained in hospital during the study period. A screening test for atopy (Tandem-E IgE; Menarini Diagnostici, Italy) was performed on cord (by direct puncture of the cord vein) and 4th day sera (using routine sampling). This assay method was modified and tested by our laboratory to discriminate very low levels of IgE (below 1 IU/ml) by progressive dilutions of the kit standards. Statistical analysis was performed by Student's t test for paired data and grouped data.
Results
The results shown in table 2 refer to the whole group of newborns and show signifi cantly higher total IgE levels in 4th day com pared to cord sera both in subjects at risk and in controls. No significant difference between serum IgE levels in the cord blood of the two groups (at risk vs. control) was found. Table 3 shows the results of the four groups of babies on different types of feeding. Cord serum IgE levels did not differ statistically in the four
Table 1. Types of feeding and subject distribution Groups
Family history
Breast milk Scrum protein hydrolyzate Soya milk Formula
positive
negative
13 20 15 68
13 20 15 67
Family history
Newborns
Cord blood
4th day blood
Significance
Positive Negative
116 115
0.52±0.37 0.51 ±0.32
0.71 ±0.48 0.66 ±0.41
p < 0.05 p < 0.05
Total
231
0.52±0.38
0.68±0.46
p < 0.05
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Prevention is generally based on the identi fication and elimination of the allergic sub stances which trigger the immunological sys tem and cause allergy. It is reasonable to assume that the use of a hypoallergenic for mula (reduced sensitizing power) during the neonatal period can decrease the incidence of atopic disease. In fact, in early childhood, feeding factors are largely responsible for al lergy development [12], The aim of the present study was to evaluate the IgE-mediated response as a predictable index of immunosensitization to different types of feed ing in the first days of life.
Groups
Family history
Cord blood
Significanee
4th day blood
Breast milk
positive negative
0.56±0.23 0.70±0.43
NS NS
0.69 ±0.35 0.70±0.34
Serum protein hydrolyzate
positive negative
0.60±0.57 0.41 ±0.35
NS NS
0.65 ±0.63 0.41 ±0.25
Soya milk
positive negative
0.54 ±0.44 0.57 ±0.46
p < 0.05 p < 0.05
0.90 ±0.39 1.10 ± 0.48
Formula
positive negative
0.50 ±0.33 0.50±0.28
p < 0.05 p < 0.05
0.73 ±0.46 0.72 ±0.42
groups, but there were significant differences in 4th day serum IgE levels. They were signifi cantly increased compared to cord blood in soya-fed and adapted formula-fed babies. This increase did not occur in neonates fed breast milk and serum protein hydrolyzate.
Discussion
The fetus is able to synthetize IgE up to 11 weeks of gestation [13] and since these anti bodies of maternal production are not able to cross the placenta [14-17], it is reasonable to suppose that the total IgE found in cord blood will be a correct evaluation of the IgE in the newborn [ 18], Fetal sensitization can occur in the uterus through the mother’s diet [19-21], It is very difficult for the mother to follow a diet which strictly avoids the most common allergenic foods (e.g. milk, eggs, fish and soya) during pregnancy and lactation and, in any case, it may not help [22-24], The interac tions between environmental factors and ge netic predetermination play a key role in the development of allergy. In a predisposed sub ject, certain foods can provoke an immune response and, in early childhood, feeding fac tors are largely responsible for allergy devel opment [4, 12], Our previous studies [25-27]
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demonstrated that babies produce IgE during the first days of life under the stimulus of feeding. Serum IgE levels arc important in diagnosing allergy although clinical manifes tation of atopy may occur in subjects with normal or low IgE levels [3, 18], IgE are essen tial in generating true atopic disease even if they are not the only trigger [3, 18], In certain pathological conditions, the IgE response is not only specific against a particular antigen, but also against other antigens not present at the time in the organism [28], A high IgE poly clonal concentration is without any clinical signs, but years later, when contact is made with one of these antigens, a large quantity of inflammatory substances is produced [2833], The use of a neonatal reduced sensitizing diet should be able to decrease the IgEmediated response and to postpone or pre vent the manifestation of atopy. In this study, we examined the effect of the type of feeding on IgE-mediated responses. The significant increase in serum IgE levels from cord to 4th day blood in babies at risk and controls does not seem to be influenced by a family history of atopy, at least during the first days of life. There was no evident cutoff in cord blood IgE levels; this parameter does not appear to be most important for identifying babies at risk. A positive family
Buonocore/Zani/Tomasini/T ripodi/ Grano/Braccl
Neonatal Prevention of Allergy
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Table 3. Serum IgE levels (IU/ml; means ± SD) in cord and 4th day blood in relation to the type of feeding
history for atopy seems to be the easiest and cheapest screening parameter [34], In the study population, the IgE levels in the group fed breast milk and serum protein hydrolyzate did not change in a significant way, and this suggests that these types of feed ing are less allergenic. The IgE levels in the groups of formula- and soya-fed babies in creased significantly, suggesting that these
formulas stimulate the immune system and IgE production in particular. In conclusion, the present results underline that it is important to start the prevention of atopic diseases in the first hours of life. The best prophylaxis for newborns at risk is breast feeding. When human milk cannot be pro vided to a newborn at risk, a hypoallergenic formula should be considered.
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