Gunnar Hattevig

Appearance of atopic disease in relation to serum IgE antibodies in children followed up from birth for 4 to 15 years

BACKGROUND Few studies have addressed the relationship between sensitization and the development of atopic disease over many years. OBJECTIVE To study the temporal relationship between the appearance of IgE antibodies in serum and atopic disease, we studied 324 children from three different groups, who were followed up prospectively from birth for 4, 12, and 15 years, respectively. METHODS Serum samples were obtained at various ages and analyzed for IgE antibodies against egg white, cows milk, wheat, animal dander, house dust mite, birch and timothy with Phadebas RAST (Kabi Pharmacia Diagnostics AB, Uppsala, Sweden) or Pharmacia CAP system. In addition, a screening test for atopy, the Phadiatop Paediatric test (Kabi Pharmacia Diagnostics AB) was performed. Presence of atopic disease was assessed by means of clinical examination, interviews, and questionnaires. RESULTS In 135 children IgE antibodies were detected at least once to at least one allergen. Antibodies to egg white appeared in 46 children before or at 2 years of age: in 57% of them IgE antibodies to inhalants developed within the next 2 years, and in 19 of 25 (76%) IgE antibodies to inhalants developed before or at 12 to 15 years. Antibodies to inhalant allergens appeared in 55 children during the first 4 years of life and in 64 before 12 to 15 years. Among the former 48% and among the latter 32% had previously detectable egg white antibodies. Atopic disease appeared before or at age 4 years in 80% of the 40 children with IgE antibodies against egg white up to 9 months of age and in 69% of the 58 children who had a positive Phadiatop Paediatric test result in infancy. CONCLUSIONS IgE antibodies in children are usually associated with current or later topic disease. Sensitization to foods in infants is usually associated with appearance of IgE antibodies to inhalants later in life.

The effect of maternal avoidance of eggs, cow's milk, and fish during lactation on the development of IgE, IgG, and IgA antibodies in infants

Serum levels of IgE, IgE antibodies to egg white (EW) and cows milk (CM), IgG, and IgA antibodies to ovalbumin (OA) and beta-lactoglobulin (BLG) were measured in a group of 115 infants with a family history of atopy/allergy at birth and at 3, 6, 9, 12, and 18 months of age. The mothers of 65 infants avoided eggs, CM, and fish during the first 3 months of lactation (maternal antigen avoidance diet, D group), whereas the remaining 50 mothers had no diet restrictions (no maternal antigen avoidance diet, ND group). CM was introduced after 6 months of age and EW after 9 months. The only statistically significant difference between the D and ND group infants was a lower rate of specimens with IgE antibodies to EW and/or CM in the infants at 3 months of age (p = 0.008). IgE antibodies to EW and/or CM appeared in 62 infants during the study period and often during complete breast-feeding. In 40 of the infants, IgE antibodies appeared before the introduction of EW and CM into the diet. The IgE concentrations of the D and the ND group infants were similar. Cord-blood IgE was a poor predictor of atopy/allergy; for example, only seven of 103 infants with double heredity for atopy/allergy had values above the 90th percentile of our normal reference. The concentrations of IgG antibodies to OA and BLG were similar in the two groups. The levels decreased significantly (p less than 0.001) from birth to 6 months of age, indicating a passive placental transfer.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of maternal dietary avoidance during lactation on allergy in children at 10 years of age

This study investigated the long‐term effects of maternal dietary avoidance during lactation on the occurrence of atopic symptoms, development of immunoglobulin E (IgE) antibodies to food and inhaled allergens and occurrence of positive skin‐prick tests (SPT) in 65 children with a family history of atopy whose mothers adhered to a diet devoid of eggs, cows milk and fish during the first 3 months of lactation (D group) and in a matched group of 50 children with mothers not practising such a diet (ND group). The diets of the D and ND children were similar. All children attended 7 follow‐ups from the age of 3 months to the age of 10 y. After the first follow‐up there was a 100% retention of participants. The results of the seventh follow‐up at 10 y are presented. Total IgE values and IgE antibodies to seven food and seven inhaled allergens were determined by the Phadebas IgE CAP® and the Phadebas RAST®, respectively. SPT were conducted for five food and seven inhaled allergens. High rates of atopic symptoms occurred in both groups, but there were no differences between the groups. Sensitization to the three foods avoided by the mothers during lactation was similar, but the overall test reactivity to foods was lower in the D group. Sensitization to inhaled allergens was similar in the two groups. During the 10 y of follow‐up, there was no difference between the groups in the occurrence of indoor furred animals, tobacco smoking, changes in heredity for atopy or development of total IgE, but a higher rate of maternal sensitization was found in the ND group, as judged by a screening test for IgE antibodies to inhalants (Phadiatop®). The results do not support general recommendations to implement prophylactic maternal dietary avoidance during lactation in allergy‐prone families.

The prevalence of allergy and IgE antibodies to inhalant allergens in Swedish school children

ABSTRACT. Out of 242 children (10 and 14 years of age) in one school‐district 221 (93 %) were evaluated for atopy/allergy by a questionnaire, interview, physical examination and determination of S‐IgE and IgE‐antibodies (RAST) to pollen, animal danders and house dust mite. Eighteen months after the initial examination all 221 children were re‐interviewed. All children with previous or current symptoms of atopy/allergy, all children with positive RAST despite a negative history and 20 non‐atopic/non‐allergic RAST‐negative children were tested with a skin prick test (SPT). At the initial examination the cumulative incidence of atopy/allergy was 32.6% and positive RAST was obtained in 40 children (18.1%). At the follow‐up the incidence of atopic/allergic symptoms during the last 18 months was 25.8%. The current prevalence of allergy to pollen and danders, assessed by interview only, was 19 % and 9 % respectively while determined by both interview and positive SPT 15 % and 5 % respectively. The mean S‐IgE (78 kU/l) of the children with current symptoms differed significantly (p<0.001) from that (19 kU/l) of the non‐atopic ones. There was no relationship between S‐IgE and the stage of puberty. Ten of the 11 children with positive RAST, but no atopy/allergy intially, developed clinical atopy/allergy during the follow‐up.

Allergy in early and late onset of atopic dermatitis

The main criteria of atopic dermatitis (AD) are based on symptoms and signs such as pruritus and age-related typical distribution and morphology of the eczema (1). AD is frequently associated with other atopic manifestations, e.g. asthma and allergic rhinoconjunctivitis (ARC), clinical allergies to, for example, pollen and danders and positive tests for allergy, e.g. RAST. AD often starts in infancy and early appearing AD and a family history of atopic disease are possible means of selecting infants at high risk for future allergy (2 , 3). In this study we have analysed if an onset of AD before two years of age implies a heavier allergy trait than AD with a later onset, by re-evaluating data from our previous prospective studies on sensitization in infants and children (2-4). One cohort of 84 girls was unselected with regard to family history of atopy (NR, normal risk), and they were followed from birth with interviews, examinations and tests at ages 3 and 8 months, and 2 ,4 ,7 and 12 years (2, 4). The initial cohort consisted of 86 children. Two nonatopic children died between 7 and 12 years. The remaining 84 children reported for all follow-up evaluations. Another cohort consisted of 115 children selected from families with atopic diseases in at least two close relatives or with single heredity and cord blood IgE 80.9 kUjl (HR, high risk) (3). The initial cohort comprised 121 children but the parents of 6 children objected to the venepunctures before or at the first follow-up examination. The remaining 1 15 children were followed from birth with interviews, examinations and tests at ages 3,6 and I8 months, and 2 and 4 years. The mothers of 65 of the 11 5 HR children were on restricted diets during lactation. The criteria of atopic manifestations and clinical allergy have been described in detail previously (2, 3). Briefly, AD was defined exclusively on the basis of its dermatological manifestations, i.e. chronic or chronically relapsing, non-infectious dermatitis of typical morphology and distribution, based on the suggestions of Hanifin 8.1 Rajka (1). Three or more episodes of bronchial obstruction were regarded as athma. Rhinitis was considered allergic if it appeared at least twice after exposure to a particular allergen. Positive exposure to an allergen was defined as an obvious reaction within 1 h on at least two occasions. The two cohorts of children were divided in three subgroups each: (group I) children with onset of AD before two years of age (12 NR children, 37 HR children); (group 11) children with onset of AD after two years of age (14 NR children, 10 HR children); and (group 111) children who did not develop AD during the period of follow-up (58 NR children, 68 HR children). IgE antibodies were determined by Phadebas Rast (Pharmacia Diagnostics AB, Uppsala, Sweden). Only IgE antibody concentrations 2 0.35 PRUjml, i.e. RAST class level 1 or higher, were regarded as positive. RAST was performed against the following allergens: egg white, cow’s milk, mite ( D . pteronyssimus), birch, timothy and mixed animal danders (cat, cow, horse, dog). The subgroups of NR and HR children were evaluated with regard to the cumulative frequencies of asthmajARC, clinical allergy to pollen or danders, positive RAST to egg white or cow’s milk, and positive RAST to inhalants. Since the samples were small and the expected frequencies were sometimes less than 5, Fisher’s exact test (two-tailed) was used to analyse possible differences between the subgroups of children. The results are shown in Table 1. For NR children the cumulative frequencies of all the markers of allergy were significantly higher in children with AD before two years of age than in children with onset of AD after two years and in children without AD. Children with onset of AD after two years did not differ from children without AD. In the HR group children with onset of AD before two years of age differed significantly from children with onset after two years only for a higher frequency of positive RAST to food antigens. Children with onset of AD before two years of age had higher frequencies of all markers of allergy than children without AD, while children with onset of AD after two years had a significantly higher frequency than children without AD only with regard to a positive RAST to inhalants.

Dextran-Reactive Antibodies in Healthy Infants and Toddlers – Relation to Type of Feeding

The appearance of dextran-reactive antibodies (DRA) during the first 2 years of life was studied in 88 healthy newborn babies in an effort to provide information about the origin of DRA in normal persons. The results were related to type of feeding, immunizations and to blood group of infants and their mothers. No DRA were detected in cord sera by passive hemagglutination. At 3 months of age 42% had DRA, at 8 months 95% and at 27 months 84%. The latter figure corresponds to previous reports of DRA in healthy adults. Peak titers were also seen at 8 months (mean 2 log titers at 3, 8 and 27 months; 2.1, 6.2 and 4.9, respectively). Breast-feeding influenced the time of appearance of DRA and the magnitude of the titers. Babies breast-fed at 3 months more often were DRA negative than those that had received cows milk-based formula at that time (p less than 0.005). However, in those breast-fed babies that were DRA positive the titers were higher than in the formula-fed infants (p less than 0.001). Other types of feeding e.g. juices did not influence the DRA levels. The appearance of DRA could not be explained by polyclonal stimulation of antibody production since changes of DRA titers in 11 tested patients could not be clearly related to similar changes of levels of antibodies to an unrelated hapten, trinitrophenyl. The study demonstrates that DRA appear during the first year of life, and that the appearance is influenced by exogenous factors. The most likely source of the antigen stimulation is the gastrointestinal flora which is altered by introduction of cows milk into the diet.

DEXTRAN‐REACTIVE ANTIBODIES IN CHILDREN Appearance during the First 4 years of Life and Relation to E. coli Infections in the Urinary Tract

ABSTRACT. The appearance of dextran‐reactive antibodies (DRA) was investigated in 88 children with sampling of serum at birth (n=87), at 3 months of age (n=87), at 8 months (n=88), at 2 years (n=86) and at 4 1/2 years of age (n=87). Serum DRA appeared at 3 months of age and a peak level exceeding the levels in adults was noted at 8 months of age. At 4 1/2 years the titres were close to those in adults. Investigation of DRA in 8 children with acute pyelonephritis and in 8 children with asymptomatic bacteriuria caused by E. coli did not indicate that the appearance of DRA was a consequence of Gram‐negative infections. The practical conclusion drawn is that if therapy with i. v. dextran is considered for infants or children, they should undergo preventive therapy with hapten dextran similar to the procedure recommended for adults.