Allergic disease at the age of 7 years after pertussis vaccination in infancy: results from the follow-up of a randomized controlled trial of 3 vaccines.

OBJECTIVE: To prospectively assess sensitization rates and the development of allergic diseases in a follow-up of a randomized controlled pertussis vaccine trial. SETTING: Two-month-old infants were the subject of this double-blind study in 1992 in a collaboration between the Pediatric Clinic and the Primary Care Centers in Linköping. PATIENTS AND INTERVENTION: Allergic diseases were evaluated in 667 children, who were randomized to 1 of 4 vaccine groups: a 2-component, a 5-component, or a whole cell pertussis vaccine (all of which were administered with the diphtheria and tetanus toxoids vaccine) and the diphtheria and tetanus toxoids vaccine alone. Allergy development was assessed by questionnaires (n = 667) and skin prick tests (n = 538) at the age of 7 years. MAIN OUTCOME MEASURES: Allergic diseases and skin prick test results at the age of 7 years. RESULTS: The cumulative incidence of allergic diseases was 34.9%, and was similar in the 4 groups (33.3%-37.3%, P =.89), even after adjusting for family history, sex, pets, dampness, environmental smoking at home, and other living conditions. Positive skin prick test results were more prevalent, however, after vaccination with the 2-component acellular vaccine (19.4%) than in the other 3 groups (11.1%-13.5%, adjusted for confounding factors, P =.01). Furthermore, allergic rhinoconjunctivitis was more common in children who were initially immunized with the 2-component pertussis vaccine and received a booster dose with an acellular vaccine compared with those who received no booster vaccination (relative risk, 3.6; 95% confidence interval, 1.1-12.0). CONCLUSION: Pertussis vaccination in infancy with any of these vaccines was not associated with allergic manifestations at the age of 7 years, apart from a higher prevalence of positive skin prick test results after an experimental 2-component vaccine, which is no longer in use.

High body mass index, asthma and allergy in Swedish schoolchildren participating in the International Study of Asthma and Allergies in Childhood: Phase II.

AIM: To assess the relationship between high body mass index (BMI) and asthma and atopic manifestations in 12-y-old children. METHODS: The relationship between high BMI and asthma symptoms was studied in 457 sixth-grade children, with (n = 161) and without (n = 296) current wheeze. High BMI was defined as > or = 75th percentile of gender-specific BMI reference values for Swedish children at 12 y of age; overweight as a subgroup of high BMI was defined as > or = 95th percentile. Children with a BMI < 75th percentile served as controls. Questionnaires were used to assess asthmatic and allergic symptoms, and bronchial hyperresponsiveness was assessed by hypertonic saline provocation tests. RESULTS: Current wheeze was associated with high BMI after adjustment for confounding factors (adjusted OR 1.7, 95% CI 1.0-2.5) and overweight had an even more pronounced effect (adjusted OR 1.9, 95% CI 1.0-3.6). In addition, asthma severity was associated with high BMI, as evaluated by the number of wheezing episodes during the previous 12 mo among the wheezing children (adjusted OR 2.0, 95% CI 1.0-4.0). There was also an association between high BMI and the presence of eczema in wheezing children (adjusted OR 2.2, 95% CI 1.0-4.6). However, high BMI was not significantly associated with hay fever, positive skin prick tests or bronchial hyperresponsiveness. CONCLUSION: The study confirms and extends a previously observed relationship between BMI and the presence of wheezing and asthma.

Hypertonic saline challenge tests in the diagnosis of bronchial hyperresponsiveness and asthma in children.

The hypertonic saline challenge test is the recommended method to assess bronchial hyperresponsiveness in the International Study of Asthma and Allergies in Childhood (ISAAC). The sensitivity of this procedure to assess asthma symptoms, however, has been reported to vary among study centers. The purpose of our study was to evaluate the value of this provocation test in an epidemiological survey in children, and to relate the degree of bronchial hyperresponsiveness to the severity of asthma symptoms. All 11-13-year-old children from 16 randomly selected schools in Linköping, Sweden received a questionnaire regarding respiratory symptoms and allergic disease. Skin prick tests with eight inhalant allergens were performed. In addition, all children with wheeze over the past 12 months (current wheeze) and a random sample of children without current wheeze were invited to perform hypertonic saline provocation tests. A complete data set was available for 170 children, including 50 with and 120 without current wheeze. Bronchial hyperresponsiveness (BHR) was defined as at least 15% decline in FEV1. The degree of BHR was represented by the response/dose ratio, i.e. the fall in FEV1 divided by total dose of inhaled saline. The severity of asthma symptoms was classified by the number of wheezing episodes over the past 12 months. 'Asthma ever' was defined by a combination of symptoms in the questionnaires. Children with 'asthma ever' and current wheeze were considered as having current asthma. Current atopic asthma was defined as current asthma with at least one positive skin prick test. The sensitivity of the procedure to detect 'asthma ever', current asthma and current atopic asthma was 62, 61 and 83%, and the specificity 83, 81 and 60%, respectively. The positive challenge rate was 52, 34, 13 and 7% among current wheezers, previous wheezers, non-wheezers with a history of allergy and healthy children. The degree of bronchial hyperresponsiveness increased with the number of wheezing episodes. Thus, the median and range of the response/dose ratio were 4.8%/ml (2.1-14.8), 2.6%/ml (0.7-8.6) and 1.3%/ml (0.8-2.7), respectively, for children with >/= 4 episodes, 1-3 episodes and no wheezing episodes over the past 12 months (p<0.001). In conclusion, hypertonic saline provocation test is useful as a tool to detect asthma in epidemiological studies in children. The degree of bronchial hyperresponsiveness, as represented by the response/dose ratio, reflects the severity of asthma symptoms.

Natural course of sensitization to cow's milk and hen's egg in childhood atopic dermatitis: ETAC study group.

BACKGROUND: Sensitization to food allergens has been implicated in the pathogenesis of atopic diseases, in particular atopic dermatitis (AD). The aim of the present paper is to investigate the natural course of sensitization to egg and to cow's milk and its relationship with the severity of AD. METHODS: The placebo intention-to-treat population of the ETACTM (Early Treatment of the Atopic Child) study consisted of 397 children with AD aged 12-24 months (mean+ SD: 17.2 + 4.1 months) who were followed for 18 months. All children were examined for objective SCORing Atopic Dermatitis (SCORAD) and specific IgE amongst other, to egg and to cow's milk at inclusion and after 3, 12 and 18 months. Fifteen patients were excluded from this analysis due to major protocol violations thus leaving 382 patients in the analysed population. RESULTS: Sensitization to egg and to cow's milk was more common in atopic children with severe AD at all time-points. At inclusion, children sensitized to both egg and to cow's milk had the most severe AD (Kruskall-Wallis test P= 0.007). The degree of sensitization expressed in RAST classes was significantly related to the severity of AD. Furthermore, children sensitized to egg or to cow's milk at inclusion had a higher risk of persistence of AD (84% and 67%, respectively, vs. 57% in those not sensitized) and a higher objective SCORAD after 18 months follow-up. CONCLUSION: We found an association between severity of AD and sensitization to egg or to cow's milk. Moreover, sensitization to egg, and to a lesser extent cow's milk, indicates a worse outcome of AD in terms of persistence and severity of the disease.

Family interaction and a supportive social network as salutogenic factors in childhood atopic illness.

The role of psycho-social factors in the development of allergy was studied prospectively in 82 infants with a family history of atopy. The family participated in a standardized family test when the children were 18 months old. The ability to adjust to demands of the situation ('adaptability'), and the balance between emotional closeness and distance ('cohesion'), were assessed from videotapes by independent raters. Families rated as functional in both of these aspects were classified as 'functional', otherwise as 'dysfunctional'. The social network, life events, atopic symptoms (based on postal inquiries regarding symptoms answered by the parents, and on physical examinations), psychiatric symptoms, and socio-economic circumstances of the families were evaluated when the children were 18 months and 3 years of age. The children were classified as atopic (asthmatic symptoms or eczema) or as non-atopic. All but two children with atopic disease at 3 years of age had atopic disease before 18 months of age, while 32 of 60 children with atopic disease at 18 months of age had no problems by 3 years of age. An unbalanced family interplay at 18 months was associated with a relative risk (RR) of 1.99 for continuing atopic illness at 3 years of age (1.18 < RR < 3.37, p = 0.01). There was a weak positive confounding effect for smoking (RR reduced by 7%), eczema on three or more localizations (RR reduced by 4.5%), and the amount of cat allergen in household dust (RR reduced by 3%). Recovery from atopic illness between 18 months and 3 years of age was four times as probable in families with functional interaction and a good social supportive network when children were 18 months of age, than in dysfunctional families with a poor social network (74% versus 20% p < 0.01). Children with asthmatic symptoms showed more signs of emotional distress than did healthy children (p = 0.02). Dysfunctional family interaction patterns were more commonly observed in families of children who at 3 years of age still had atopic symptoms, than in children who had recovered. The patterns included expression of emotion and reaction to the needs of others, alternating between total disinterest and over-involvement (p = 0.02), lack of support and rejection of offered support (p = 0.01), a greater number of individual decisions without regard to the other family members (p = 0.04), and indistinct 'generational boundaries' (p = 0.04). We conclude that psychosocial factors, such as family interaction and a supportive social network, play a significant role in the course of atopic illness in early childhood and that measures which enhance family interaction and the social network could influence the course of the disease favorably.

Hypoallergenicity of an extensively hydrolyzed whey formula.

Several different protein hydrolysate-based infant formulas have been promoted as hypoallergenic and considered suitable for the dietary management of cow's milk allergy (CMA). Accepting that none of the hydrolysate-based products is completely safe, the American Academy of Pediatrics (AAP) recommends that these formulas should be tested in a double-blind placebo-controlled setting and tolerated by at least 90% of children with proven CMA. In principle, this recommendation is also endorsed by the European Society of Paediatric Gastroenterology and Nutrition (ESPGAN) and the European Society of Paediatric Allergy and Clinical Immunology (ESPACI). In this two-center study, 32 children with proven CMA were tested with the extensive hydrolysate whey formula Nutrilon Pepti, for comparison with Profylac (extensive) and Nan HA (partial) whey hydrolysate products. Skin-prick tests (SPTs) were, respectively, positive to the three hydrolysate formulas in 19%, 15%, and 32% of children. After oral challenge it was concluded that 97% (95% CI: 85-100%) of the children tolerated Nutrilon Pepti, 94% (95% CI: 75-100%) tolerated Profylac, and 64% (95% CI: 37-81%) tolerated Nan HA. This study demonstrates that the extensive hydrolysates Nutrilon Pepti and Profylac are well tolerated in a population of children with proven CMA and that both products can be considered safe for their intended use. This study confirms that a very small number of children react even to extensively hydrolyzed formulas. SPT prior to oral exposure to the hydrolysate-based formulas can indicate whether a child is at risk of showing reactions to the product. Introduction of new products to these children should be carried out under a doctor's supervision. However, the majority of the SPT-positive children did tolerate the two extensively hydrolyzed whey-based formulas tested.

Atopy among schoolchildren in northern and southern Sweden in relation to pet ownership and early life events.

Studies have suggested a higher prevalence of asthma and allergies in northern, as compared to southern, Scandinavia. The aim of this study was to evaluate regional differences in atopy in relation to pet ownership and certain early life events among schoolchildren (n=2108) aged 10-11 years from Linköping in southern Sweden and Ostersund in northern Sweden. The parents completed a questionnaire, comprising questions on home environment, heredity, socio-economic conditions, and the core questions on symptoms from the International Study of Asthma and Allergies in Childhood. The children were skin-prick tested to eight common inhalant allergens. Information on maternal smoking habits, gestational age, and anthropometric measures were obtained from the Swedish Medical Birth Registry. The prevalence of atopic symptoms and sensitization to pollen were similar in Ostersund and in Linköping. A higher prevalence of sensitization to animal dander among children in Ostersund could be linked to a higher occurrence of pets in the community. Current cat ownership was related to less sensitivity to cat allergen but only in children with an atopic heredity. Ponderal index >30 kg/m3 was related to an increased risk of atopic sensitization, both in Linköping (adjusted odds ratio 2.1; 95% confidence interval 1.1-4.0) and in Ostersund (adjusted odds ratio 2.0; 95% confidence interval 1.1-3.5). Maternal smoking during pregnancy was related to an increased risk of atopic sensitization among children in Linköping, whereas current smoking was associated with a decreased risk of sensitization in Ostersund. In conclusion, we demonstrated that a high occurrence of pets in the community was associated with sensitization, whereas atopic symptoms were essentially unaffected. This study has also suggested an association between body size at birth and atopic sensitization at 10-11 years of age.

Development of immunoglobulin G and immunoglobulin E antibodies to cow's milk proteins and ovalbumin after a temporary neonatal exposure to hydrolyzed and whole cow's milk proteins.

The ingestion of food antigens usually results in the induction of oral tolerance, but the clinical and immunologic consequences of brief exposure to cow's milk proteins during the neonatal period are not well-documented. The aim of this work was to study immunoglobulin (Ig)E and IgG responses to cow's milk proteins and ovalbumin after exposure during the first three days of life in infants who were otherwise exclusively breast-fed. A group of 129 infants was randomly assigned at birth to one of three feeding regimens: human milk (HM), cow's milk formula (CMF), or a casein hydrolysate formula (CHF), during the first three days of life. They were then all exclusively breast-fed for a varying period of time and followed for two years. Serum IgG and IgE antibodies to cow's milk proteins and ovalbumin (OVA) were analyzed in blood samples obtained at birth, at 4 days and at 2, 4, 8, 12 and 24 months of age. The levels of IgG antibodies to beta-lactoglobulin (IgG-BLG) and bovine serum albumin (IgG-BSA) were higher in the CMF and the HM groups than in the CHF group for up to two years. This was particularly obvious for IgG-BLG in infants who started weaning before two months. The levels of IgG antibodies to casein (IgG-CAS) were higher in the CMF group, as compared with the CHF group at 8 and 12 months. The levels of IgG antibodies to OVA were similar in all three feeding groups. The levels of IgE antibodies to CAS or OVA were similar in the three feeding groups. Exposure to cow's milk during the first three days of life stimulated IgG antibody production to cow's milk proteins and this was still obvious at 2 years of age, while feeding with a casein hydrolysate during the first three days of life was associated with low levels of IgG antibodies to cow's milk proteins.

Mite fauna in the home and sensitivity to house-dust and storage mites.

In search of potential new indoor allergen sources, all mites in dust from homes of 55 asthmatic children living in three climatic regions in Sweden were counted and identified by light microscope. Antibodies of the IgE class against three house-dust mites and three storage mites were measured in corresponding serum samples. Mites were found in all but two homes from the northernmost area, where levels also were lower than in the other regions. The highest mite densities were most often found in bedrooms (50%) and living rooms (40%). Mite density was increased in homes with high humidity and was higher in bungalows than in flats. House-dust mites predominated in the south and storage mites in the east central area, particularly in kitchens and bathrooms. Mite-density and IgE-antibody levels against house-dust mites were significantly associated. The same association applied to storage mites. Other species numbered around 100 mites/g dust in some homes. Microscopy helps to identify potentially important mites. Analysing home dust only for house-dust mites will underestimate mite exposure. Storage mites may be as relevant to sensitivity as house-dust mites. As other species occasionally were found in high numbers, their relevance should also be assessed.

Allergic disease in teenagers in relation to urban or rural residence at various stages of childhood.

BACKGROUND: Higher prevalences of allergic diseases and IgE antibodies to inhalant allergens have been reported for persons living in urban areas than for persons living in rural areas. METHODS: Associations between cumulative incidences of allergic diseases in 1878 children aged 13-14 years and their place of residence (urban, semiurban, or rural) from birth were assessed by questionnaire (ISAAC), in order to find out whether there is a period of increased sensitivity to external influences during the first few years of life. Family history and exposure to pets, tobacco smoke, and damp were considered in multiple regression. RESULTS: There was a significantly higher prevalence of allergic diseases with urban residence than with rural residence during the first 2 years of life (e.g., for bronchial asthma, relative risk (RR) for the first year 2.1, 95% CI 1.2-3.7). An increased risk was still found after multiple regression (RR=1.7). Semiurban residence was associated with an intermediate cumulative incidence of allergic diseases. Maternal smoking during pregnancy was associated with asthma (RR=1.4, 95% CI 1.0-2.0). CONCLUSIONS: The findings support a period of increased susceptibility during the first years of life. Whether rural lifestyle protects against allergy or whether urban pollutants contribute to allergy has to be elucidated [corrected].

Is allergy prevention realistic and beneficial?

Allergic diseases among children have shown a marked increase during the last two or three decades, despite increased awareness of possible preventive measures. Preventive efforts have focused on new-borns and infants with a biparental history of allergy as they are at particularly high risk of developing allergic disease (40-60%). No good intervention studies have been performed in the general population, only in high-risk families. Unfortunately, so far known risk factors can only explain a small part of the recent increase in allergic diseases. The most important recommendation for everyone is not to smoke during pregnancy and when living/working with young children. Breast milk is the best for every baby, even from an immunologic aspect. Humidity problems should be reduced in homes, day-care centres and schools. It is probably wise not to keep furred pets indoors in homes when babies have a family history of allergy. However, the effect of such advice should be assessed, including the acceptability, compliance, costs and effectiveness. There is no doubt that we should go on with preventive measures both in babies at high risk of allergy and also in the general population. At the same time, research should try to find even more efficient ways to reduce the current "allergy epidemic".

A genome-wide search for linkage to asthma. German Asthma Genetics Group.

Asthma is among the most frequent chronic diseases in childhood. Although numerous environmental risk factors have already been identified, the basis for familial occurrence of asthma remains unclear. Previous genome screens for atopy in British/Australian families and for asthma in different American populations showed inconsistent results. We report a sib pair study of a sample of 97 families, including 415 persons and 156 sib pairs. Following an extensive clinical evaluation, all participants were genotyped for 351 polymorphic dinucleotide markers. Linkage analysis for asthma identified four chromosomal regions that could to be linked to asthma: chromosome 2 (at marker D2S2298, P = 0.007), chromosome 6 (around D6S291, lowest P = 0.008), chromosome 9 (proximal to D9S1784, P = 0.007), and chromosome 12 (D12S351, P = 0.010). These linkage regions could be reproduced for all loci by analysis of total or specific immunoglobulin E (minimum P values at these regions were 0. 003, 0.001, 0.010, and 0.015, respectively).

A randomized controlled trial of the effect of pertussis vaccines on atopic disease.

BACKGROUND: Pertussis vaccination in infancy has been suggested to increase the risk for development of asthma and allergy. OBJECTIVE: To assess sensitization rates and development of atopic diseases in a prospective randomized controlled trial of pertussis vaccine. PATIENTS AND METHODS: A total of 669 children were randomized to 1 of 4 vaccine groups (2-component acellular pertussis, 5-component acellular pertussis, whole-cell pertussis vaccines, and placebo [diphtheria and tetanus toxoids]). Diphtheria and tetanus toxoids were also given to the children in the pertussis vaccine groups. The children were evaluated by means of questionnaires at age 2 months, 7 months, and 2 1/2 years; skin prick tests at age 7 months and 2 1/2 years; and blinded clinical investigation at age 2 1/2 years. The families were contacted at regular intervals to assess possible adverse effects after the vaccinations and symptoms of whooping cough. RESULTS: The cumulative incidence of atopic diseases was 30% and incidence rates were similar in the 4 groups after adjusting for family history. Exposure to environmental tobacco smoke and home dampness did not confound these results. The frequency of adverse effects did not differ appreciably between atopic and nonatopic children, with the exception that a nodule at the vaccination site was more frequent after whole-cell pertussis vaccination in the nonatopic children. Among 47 children with proven pertussis, atopic disease appeared in 19 (40%). Of these 47 children, 9 (19%) developed asthma, as compared with 58 (9%) noninfected children (P=.03). CONCLUSIONS: We found no support for a drastic increase in allergic manifestations after pertussis vaccination. There was a positive association between whooping cough and asthma by 2 1/2 years of age. There seems to be little reason to withhold pertussis vaccination from infants, irrespective of family history of allergy.

Environmental assessment of Dermatophagoides mite-allergen levels in Sweden should include Der m 1.

The major allergen of Dermatophagoides microceras, Der m 1, as well as the allergens of D. pteronyssinus and D. farinae, Der p 1 and Der f 1, were analyzed in the homes of 111 asthmatic children in three climatic regions in Sweden. The numbers and species of mites were determined by microscopy, and circulating IgE antibodies against mites were measured. Der f 1 was the predominant house-dust-mite (HDM) allergen, Der p 1 the least often found, and Der m 1 represented 31% of the allergen load. However, in the Linköping area, Der m 1 was the major HDM allergen (58%). Mite counts and allergen levels correlated well. Current exposure to HDM allergens at home was associated with the serum IgE antibody response to HDM in the children with no threshold level. Of the children with IgE antibodies against HDM, 67% reacted to all three mites. Mite sensitization rates were marginally increased (7%) by the addition of IgE analysis of D. microceras to the routine analysis of IgE antibodies against D. pteronyssinus and D. farinae. Thus, Der m 1 may be an important HDM allergen and should be considered when HDM exposure data are assessed in areas with a climate like that of Sweden.

Pertussis IgE and atopic disease.

BACKGROUND: Pertussis toxin (PT) stimulates IgE production in animals, and pertussis vaccination and whooping cough may have similar effects in man. METHODS: We analyzed IgE responses to PT (PT-IgE) in sera from children primarily immunized with three doses of either an acellular 2- or 5-component vaccine, or a whole-cell (Wc) pertussis vaccine, and in children after whooping cough. The study comprised 50 children with both atopic disease and positive skin prick test, 99 nonatopic controls, and 40 children with verified pertussis. RESULTS: Immunoglobulin E antibodies against PT were demonstrated in 19% and 24% of sera from vaccinated children at 7 and 12 months, respectively, and in 9% at 2.5 years. At 7 months, PT-IgE was more common after vaccination with acellular (24%) than with the Wc vaccine (3%, P = 0.02). PT-IgE was also more common (P = 0.001) after vaccination in children classified as atopic (36%) than in the control group (10%). Thirty percent of the children with pertussis had PT-IgE, more often so in atopic than nonatopic children (P = 0.02). CONCLUSIONS: Transient production of PT-IgE seems to be common after primary pertussis immunization with acellular vaccines, and after whooping cough, particularly in atopic subjects.

Exposure to indoor allergens in early infancy and sensitization.

BACKGROUND: Indoor allergens play a major role both in sensitization and as triggers of asthma in children. The relationship between allergen exposure and sensitization to cats, dogs, and mites was studied prospectively in 100 newborn babies with a history of allergy in both parents. METHODS: Skin prick tests were done with Dermatophagoides pteronyssinus, D.farinae, and cat and dog allergens in all the children at 6 and 18 months of age and in 86 children at 5 years of age. Dust samples were collected from the homes during infancy and at 5 years. The parents of the children responded to a questionnaire focused on environmental factors that could influence indoor allergen levels. In addition, dust samples were collected from the day-care centers of the sensitized children. The allergen levels were determined by ELISA. RESULTS: The levels of the major cat allergen, Fel d 1, varied from 0.02 microg to 6.8 microg/gm (geometric mean [GM], 0.4 microg/gm) during infancy and less than 0.02 microg to 13 microg/gm dust (GM, 0.12 microg/gm) at age 5 years. Dog allergen, Can f 1, levels ranged from 0.18 microg to 590 microg/gm (GM, 3.1 microg/gm) in infancy and 0.09 microg to 13 microg/gm at age 5 years (GM, 0.6 microg/gm). Eleven children (13%) were sensitive to cats, and three were sensitive to dogs at 5 years of age. They had been exposed to similar levels of allergen as the nonsensitized children. The levels of mite allergen (Der p 1 + Der f 1) at age 1 year varied from less than 0.02 microg to 1 microg/gm dust (GM, 0.12 microg/gm) and at age 5 years from less than 0.02 microg to 3.5 microg/gm (GM, 0.05 microg/gm) dust. Only two homes contained mite allergen levels greater than 2 microg/gm dust. The levels were less than 0.3 microg/gm dust in all but one sample from the day-care centers. Only one child was sensitized to mites at age 5 years. The mite allergen level was less than 0.1 microg/gm at home, and he did not attend a day-care center. CONCLUSIONS: The findings indicate that exposure to low levels of indoor allergens in early childhood is associated with a low incidence of sensitization. However, levels well below currently suggested threshold levels may cause sensitization in children with a family history of allergy. We suggest that a fixed threshold risk level for allergic sensitization may not be appropriate in all climates.

Parity among atopic and non-atopic mothers.

A temporary Th2 skewed immunity is essential for a successful outcome of pregnancy. It is also a hallmark of atopic disease. We recorded the number of siblings to 3667 children in relation to maternal atopy. In all, 65% of the allergic and 56% of the non-allergic mothers had more than one child (p < 0.001). These data support a hypothesis that the atopic genotype may be associated with an increased likelihood for a successful outcome of pregnancy and thus from an evolutionary point of view compensate for the less efficient host defence against microbial infections associated with this type of immunity.