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.

1 Kjcllman NIM: Food allergy - Epi­ demiology and prediction; in Harms HK, Wahn U (eds): Food Allergy in Infancy and Childhood. Berlin. Springer 1989. pp 205-207. 2 Kajosaari M: Food allergy in Fin­ nish children aged one to six years. Acta Paediatr Scand 1982:71:815819. 3 Hamburger RN: The immunogenetics of IgE provides predictive value for the development of allergy. Ann Allergy 1982;49:9-11. 4 Allievi E, l.ino S, Palumbo-Vargas O. Vaccari A: Studio controllato sull’importanza della dieta nel pre­ venire manifestazioni allergiche in neonati a rischio di atopia. Folia Allergol Immunol Clin 1989:36:127— 137. 5 Businco L, Marchetti F. Pellegrini G, Cantani A, Perlini R: Prevention of atopic disease in ‘at risk' new­ borns by prolonged breast-feeding. Ann Allergy 1983;51:296-299. 6 HattevigG. Kjcllman NIM, Bjorksten R. Johansson SGO: The preva­ lence of allergy and IgE antibodies to inhalant allergens in Swedish school children. Acta Paediatr Scand 1987:76:349-355. 7 Cavagni G. Rondini G: Consider­ ation on preventive strategies of childhood food allergy. Riv Ital Pediatr 1990;16:377-382. 8 IIjaltc K. Croner S. Kjellman NIM: Cost-effectiveness of neonatal IgE screening for atopic allergy before 7 vears of age. Allergy 1987:42:97— 103.

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Businco L: Atopia nella prima infanzia. Immunol Pcdiatr 1931; 1:4— 49. Young P: Asthma and allergies: An optimistic future. US Dept of Health and Human Services, Public Health Service N il! Publication 1980:30:388-442. Michel FB. Bousquet J. Coulomb U: Prediction of the high-allergic risk newborn; in Johansson SGO (ed): Diagnosis and Treatment of IgE Me­ diated Diseases. Amsterdam, Excerpta Medica. 1981. pp 35-37. Marsh DG. Meyers DA: The epide­ miology and genetics of atopic aller­ gy. N Engl J Med 1981:305:15511570. Miller DL. Hirvonen T. Gitlin D: Synthesis of IgE by the human con­ c e p ts . J Allergy Clin Immunol 1973:52:182-190. Bazaral M. Orgel HA. Hamburger RN: IgE levels in normal infants and mothers and an inheritance hypoth­ esis. J Immunol 1971:107:794-801. Berg T: The immunoglobulin devel­ opment during the first year of life. Acta Pediatr Scand 1979:58:229— 242. Kuhns WJ: Studies of immediate wheal reactions and of readme anti­ bodies in pregnancy and in the new­ born infant. Proc Soc Exp Biol Med 1965:118:337-380. GaburroD . Piacentini G. Boner AL: Immunological aspects of food al­ lergy prevention. Riv Ital Pediatr 1990:16:383-390.

18 Bousquet J, Menardo JL, Viala JL, Michel FB: Predictive value of cord serum IgE determination in the de­ velopment of ‘early-onsct’ atopy. Ann Allergy 1983;51:291-295. 19 Chandra RK. Puri S. Cheema PS: Predictive value of cord blood IgE in the development of atopic disease and role of breast feeding in its pre­ vention. Clin Allergy 1985:15:517— 522. 20 Chandra RK: Environmental engi­ neering in the prevention o f atopic disease: How early is early enough: in Chandra RK (ed): Food Allergy. Saint John’s. Nutrition Research Education Foundation. 1987. pp 373-387. 21 Falth-Magnusson K, Kjellman NIM: Development of atopic disease in babies whose mothers were on ex­ clusion diet during pregnancy. A randomized study. J Allergy Clin Immunol 1987;80:868-875. ’ 22 Kjellman NIM. Bjorksten B: Mater­ nal interaction with her fetus/infants and childhood allergy. Proc XIV Congr Eur Acad Allergol Clin Immunol. Berlin, 1989. pp 180181. 23 Jakobson I. LindbergT: Bencdiktssson B: Dietary bovine beta-globulin is transferred to human milk. Acta Paediatr Scand 1985;74:341-345. 24 Falth-Magnusson K. Aman H. Kjellmann NIM: Maternal abstention from cow’s milk and egg in allergy' risk pregnancies. Effect of antibody production in the mother and in the newborn. Allergy 1987:42:64-73.

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References

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Serum IgE concentrations in the neonatal period.

The aim of the present study was to evaluate the IgE-mediated response as a predictable index of immunosensitization to different types of feeding (br...
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