Predicting food allergy: The value of patient history reinforced.

BACKGROUND: EAACI guidelines emphasize the importance of patient history in diagnosing food allergy (FA) and the need for studies investigating its value using standardized allergy-focused questionnaires. OBJECTIVE: To determine the contribution of reaction characteristics, allergic comorbidities and demographics to prediction of FA in individuals experiencing food-related adverse reactions. METHODS: Adult and school-age participants in the standardized EuroPrevall population surveys, with self-reported FA, were included. Penalized multivariable regression was used to assess the association of patient history determinants with "probable" FA, defined as a food-specific case history supported by relevant IgE sensitization. RESULTS: In adults (N = 844), reproducibility of reaction (OR 1.35 [95% CI 1.29-1.41]), oral allergy symptoms (OAS) (4.46 [4.19-4.75]), allergic rhinitis (AR) comorbidity (2.82 [2.68-2.95]), asthma comorbidity (1.38 [1.30-1.46]) and male sex (1.50 [1.41-1.59]) were positively associated with probable FA. Gastrointestinal symptoms (0.88 [0.85-0.91]) made probable FA less likely. The AUC of a model combining all selected predictors was 0.85 after cross-validation. In children (N = 670), OAS (2.26 [2.09-2.44]) and AR comorbidity (1.47 [CI 1.39-1.55]) contributed most to prediction of probable FA, with a combined cross-validation-based AUC of 0.73. When focusing on plant foods, the dominant source of FA in adults, the pediatric model also included gastrointestinal symptoms (inverse association), and the AUC increased to 0.81. CONCLUSIONS: In both adults and school-age children from the general population, reporting of OAS and of AR comorbidity appear to be the strongest predictors of probable FA. Patient history particularly allows for good discrimination between presence and absence of probable plant FA.

Prevalence of Food Sensitization and Food Allergy in Children Across Europe.

BACKGROUND: For adults, prevalence estimates of food sensitization (FS) and food allergy (FA) have been obtained in a standardized manner across Europe. For children, such estimates are lacking. OBJECTIVES: To determine the prevalence of self-reported FA, FS, probable FA (symptoms plus IgE sensitization), and challenge-confirmed FA in European school-age children. METHODS: Data on self-reported FA were collected through a screening questionnaire sent to a random sample of the general population of 7- to 10-year-old children in 8 European centers in phase I of the EuroPrevall study. Data on FS and probable FA were obtained in phase II, comprising an extensive questionnaire on reactions to 24 commonly implicated foods, and serology testing. Food challenge was performed in phase III. RESULTS: Prevalence (95% CI) of self-reported FA ranged from 6.5% (5.4-7.6) in Athens to 24.6% (22.8-26.5) in Lodz; prevalence of FS ranged from 11.0% (9.7-12.3) in Reykjavik to 28.7% (26.9-30.6) in Zurich; and prevalence of probable FA ranged from 1.9% (0.8-3.5) in Reykjavik to 5.6% (3.6-8.1) in Lodz. In all centers, most food-sensitized subjects had primary (non-cross-reactive) FS. However, FS due to birch pollen related cross-reactivity was also common in Central-Northern Europe. Probable FA to milk and egg occurred frequently throughout Europe; to fish and shrimp mainly in the Mediterranean and Reykjavik. Peach, kiwi, and peanut were prominent sources of plant FA in most countries, along with notably hazelnut, apple, carrot, and celery in Central-Northern Europe and lentils and walnut in the Mediterranean. CONCLUSIONS: There are large geograhical differences in the prevalence of FS and FA in school-age children across Europe. Both primary and cross-reactive FS and FA occur frequently.

Predictors of Food Sensitization in Children and Adults Across Europe.

BACKGROUND: The geographical variation and temporal increase in the prevalence of food sensitization (FS) suggest environmental influences. OBJECTIVE: To investigate how environment, infant diet, and demographic characteristics, are associated with FS in children and adults, focusing on early-life exposures. METHODS: Data on childhood and adult environmental exposures (including, among others, sibship size, day care, pets, farm environment, and smoking), infant diet (including breast-feeding and timing of introduction to infant formula and solids), and demographic characteristics were collected from 2196 school-age children and 2185 adults completing an extensive questionnaire and blood sampling in the cross-sectional pan-European EuroPrevall project. Multivariable logistic regression was applied to determine associations between the predictor variables and sensitization to foods commonly implicated in food allergy (specific IgE ≥0.35 kUA/L). Secondary outcomes were inhalant sensitization and primary (non-cross-reactive) FS. RESULTS: Dog ownership in early childhood was inversely associated with childhood FS (odds ratio, 0.65; 95% CI, 0.48-0.90), as was higher gestational age at delivery (odds ratio, 0.93 [95% CI, 0.87-0.99] per week increase in age). Lower age and male sex were associated with a higher prevalence of adult FS (odds ratio, 0.97 [95% CI, 0.96-0.98] per year increase in age, and 1.39 [95% CI, 1.12-1.71] for male sex). No statistically significant associations were found between other evaluated environmental determinants and childhood or adult FS, nor between infant diet and childhood FS, although early introduction of solids did show a trend toward prevention of FS. CONCLUSIONS: Dog ownership seems to protect against childhood FS, but independent effects of other currently conceived environmental and infant dietary determinants on FS in childhood or adulthood could not be confirmed.

Comparative Study of Food Allergies in Children from China, India, and Russia: The EuroPrevall-INCO Surveys.

BACKGROUND: A clear understanding of the differences in the epidemiology of food allergy between rural and urban populations may provide insights into the causes of increasing prevalence of food allergy in the developed world. OBJECTIVE: We used a standardized methodology to determine the prevalence and types of food-specific allergic sensitization and food allergies in schoolchildren from urban and rural regions of China, Russia, and India. METHODS: The current study is a multicenter epidemiological survey of children recruited from 5 cities in China (Hong Kong and Guangzhou), Russia (Tomsk), and India (Bengaluru and Mysore) and 1 rural county in Southern China (Shaoguan). A total of 35,549 children aged 6 to 11 years from 3 countries participated in this survey. Random samples of children from 3 countries were first screened by the EuroPrevall screening questionnaire. Children with and without a history of adverse reactions to foods were then recruited for the subsequent case-control comparative studies. We determined the prevalence rates of food-specific IgE sensitization and food allergies using the predefined criteria. RESULTS: The prevalence rates of food-specific IgE sensitization (≥0.7 kU/L) to at least 1 food were 16.6% in Hong Kong, 7.0% in Guangzhou, 16.8% in rural Shaoguan, 8.0% in Tomsk, and 19.1% in India. Using a definition of probable food allergy as reporting allergic symptoms within 2 hours of ingestion of a specific food plus the presence of allergic sensitization to the specific food (positive IgE and/or positive skin prick test result), the prevalence of food allergy was highest in Hong Kong (1.50%), intermediate in Russia (0.87%), and lowest in Guangzhou (0.21%), Shaoguan (0.69%), and India (0.14%). For children recruited from Hong Kong, both sensitization and food allergy were significantly higher in children who were born and raised in Hong Kong when compared with those who were born in mainland China and migrated to Hong Kong, highlighting the importance of early-life exposures in affecting the subsequent development of food sensitization and food allergy. CONCLUSIONS: There are wide variations in the prevalence of food-specific IgE sensitization and food allergy in the 3 participating countries. Food allergy appears to be less common when compared with developed countries. The variations in the prevalence of food allergen sensitization cannot be explained by the differences in the degree of urbanization. Despite the high prevalence of food-specific IgE sensitization in India and rural China, food allergy is still extremely uncommon. In addition to IgE sensitization, other factors must play important roles resulting in the clinical manifestations of food allergies.

Food Allergy in Adults: Substantial Variation in Prevalence and Causative Foods Across Europe.

BACKGROUND: According to the community-based EuroPrevall surveys, prevalence of self-reported food allergy (FA) in adults across Europe ranges from 2% to 37% for any food and 1% to 19% for 24 selected foods. OBJECTIVE: To determine the prevalence of probable FA (symptoms plus specific IgE-sensitization) and challenge-confirmed FA in European adults, along with symptoms and causative foods. METHODS: In phase I of the EuroPrevall project, a screening questionnaire was sent to a random sample of the general adult population in 8 European centers. Phase II consisted of an extensive questionnaire on reactions to 24 preselected commonly implicated foods, and measurement of specific IgE levels. Multiple imputation was performed to estimate missing symptom and serology information for nonresponders. In the final phase, subjects with probable FA were invited for double-blind placebo-controlled food challenge. RESULTS: Prevalence of probable FA in adults in Athens, Reykjavik, Utrecht, Lodz, Madrid, and Zurich was respectively 0.3%, 1.4%, 2.1%, 2.8%, 3.3%, and 5.6%. Oral allergy symptoms were reported most frequently (81.6%), followed by skin symptoms (38.2%) and rhinoconjunctivitis (29.5%). Hazelnut, peach, and apple were the most common causative foods in Lodz, Utrecht, and Zurich. Peach was also among the top 3 causative foods in Athens and Madrid. Shrimp and fish allergies were relatively common in Madrid and Reykjavik. Of the 55 food challenges performed, 72.8% were classified as positive. CONCLUSIONS: FA shows substantial geographical variation in prevalence and causative foods across Europe. Although probable FA is less common than self-reported FA, prevalence still reaches almost 6% in parts of Europe.

Food allergy in the Netherlands: differences in clinical severity, causative foods, sensitization and DBPCFC between community and outpatients.

BACKGROUND: It is unknown whether food allergy (FA) in an unselected population is comparable to those from an outpatient clinic population. OBJECTIVE: To discover if FA in a random sample from the Dutch community is comparable to that of outpatients. METHODS: This study was part of the Europrevall-project. A random sample of 6600 adults received a questionnaire. Those with symptoms to one of 24 defined priority foods were tested for sIgE. Participants with a positive case history and elevated sIgE were evaluated by double-blind placebo-controlled food challenge (DBPCFC). Outpatients with a suspicion of FA were evaluated by questionnaire, sIgE and DBPCFC. RESULTS: In the community, severe symptoms were reported less often than in outpatients (39.3% vs. 54.3%). Participants in the community were less commonly sensitized to any of the foods. When selecting only those with a probable FA (i.e. symptoms of priority food and elevation of sIgE to the respective food), no major differences were observed with respect to severity, causative foods, sensitization and DBPCFC between the groups. CONCLUSION: In the Netherlands, there are large differences in self-reported FA between community and outpatients. However, Dutch community and outpatients with a probable FA do not differ with respect to severity, causative foods, sensitization and DBPCFC-outcome.

Influence of alternative lifestyles on self-reported body weight and health characteristics in women.

BACKGROUND: Alternative lifestyles are often associated with distinct practices with respect to nutrition, physical activity, smoking, alcohol use and usage of complementary medicine. Evidence concerning effects of these lifestyle-related practices on health status is still fragmentary. OBJECTIVE: To describe maternal health characteristics related to alternative lifestyles, with emphasis on body-weight status, during pregnancy and maternity periods. METHODS: We compared self-reported health-related features of mothers with alternative lifestyles and conventional lifestyles during pregnancy and maternity period in the KOALA Birth Cohort Study. This cohort comprises two recruitment groups of mother-infant pairs, one with a conventional (no selection based on lifestyle, n = 2333), the other with an alternative lifestyle (selected via organic food shops, anthroposophic clinicians and midwives, anthroposophic under-five clinics, Rudolf Steiner schools and relevant magazines, n = 485). Mothers in the alternative group more frequently chose organic foods, adhered to specific living rules, practised vegetarianism and identified themselves with anthroposophy. RESULTS: Mothers in the alternative group showed lower BMI and lower prevalence of overweight and obesity than the conventional group, before pregnancy as well as 4-5 years after delivery. This difference was partly retained after adjusting for potential confounders. Furthermore, women in the alternative group had a lower prevalence of pregnancy-related hypertension, more often started breastfeeding and gave exclusive and prolonged breastfeeding for a longer period. Finally, they smoked less often, but more often drunk alcohol during pregnancy. CONCLUSION: The results suggest that an alternative lifestyle is associated with favourable body weight and with several differences in other health features.

The association between foodborne and orofecal pathogens and allergic sensitisation -- EuroPrevall study.

BACKGROUND: An inverse association between markers of exposure to foodborne and orofecal pathogens and allergic sensitization has been reported. However, the findings of epidemiological studies have not been consistent. This study investigated the relationship between antibodies to hepatitis A, Toxoplasma gondii and salmonella and allergic sensitization to food and aeroallergens in children from different geographical areas. METHODS: Specific IgE and/or skin prick testing against food and aeroallergens were measured in children from 6 to 12 years of age residing in Greece, the Netherlands, China, India and Russia. Seropositivity to the three pathogens was measured, and data on potential confounders were collected using questionnaire. RESULTS: Data from 800 children (126 from Athens; 248 from Utrecht; 110 from Hong Kong; 119 from urban Tomsk; and 197 from rural Tomsk) could be analysed. The highest percentage of positive serology to salmonella was found in Hong Kong (46.4%), to T. gondii in urban Tomsk (13.4%) and to hepatitis A in Athens (71.2%). Although not significant, T. gondii seropositivity tends to be negatively associated, and hepatitis A seropositivity tends to be positively associated with allergic sensitization. CONCLUSION: Inconsistent associations were observed between allergic sensitization to food and aeroallergens and markers of exposure to two common foodborne pathogens. The association with T. gondii tends to be negative, consistent with the 'hygiene hypothesis', but the association with hepatitis A tends to be positive. Taken together, there is no clear evidence that past exposure to foodborne and orofecal pathogens protects against allergic sensitization to food or aeroallergens.

EuroPrevall survey on prevalence and pattern of self-reported adverse reactions to food and food allergies among primary schoolchildren in Vilnius, Lithuania.

The aim of the research was to assess the prevalence and pattern of self-reported adverse reactions to food and food allergies among primary schoolchildren in Vilnius. MATERIAL AND METHODS. Vilnius University was a partner in the EuroPrevall project. A total of 4333 schoolchildren from 13 primary schools participated in the study. Of all 4333 questionnaires distributed, 3084 were returned (response rate, 71.2%). This screening phase was followed by the second (clinical) part with an objective confirmative laboratory analysis of blood samples for the diagnosis of food allergy. For the research purposes, 186 blood samples for IgE were analyzed. RESULTS. Almost half of the children had an illness or a disorder caused by eating food. The prevalence of adverse reactions to food was found to be increasing with age from 6 to 10 years. Food allergy was diagnosed in 16.4% of children. Boys had food allergy more frequently than girls. Diarrhea or vomiting and a rash, urticarial rash, or itchy skin were the most commonly mentioned symptoms. Fruits, berries, and milk and dairy were found to be the most common foods to cause adverse reactions. The most relevant foods for children with IgE-mediated food allergy were cow's milk and hazelnuts. CONCLUSIONS. The prevalence of self-reported food hypersensitivity among primary schoolchildren was observed in almost half of the studied population. Fruits, berries, and milk and dairy were the most common foods to cause adverse reactions among primary schoolchildren in Lithuania. The determined differences in the prevalence of food hypersensitivity and IgE-mediated food allergy and associations with gender and age need further scientific analysis for the development of prognostic and diagnostic tools.

Effect of area of residence on patterns of aeroallergen sensitization in atopic patients.

BACKGROUND: An association with sensitization to inhaled allergens and allergic rhinitis and asthma has been established. A recent study concluded that the disparity in allergen sensitization might primarily be caused by environmental factors rather than genetic differences. The primary objective was to identify potential differences in sensitization among subjects with the same ethnicity in South India who reside in different environments. METHODS: Five hundred forty-six patients presenting to a tertiary allergy center with allergic rhinitis and or asthma underwent evaluation using a structured questionnaire, skin-prick testing to common aeroallergens, and spirometry and were categorized according to area of residence. RESULTS: The most common allergens causing sensitization were house-dust mite (range, 65-70%), trees (range, 52-56%), and cockroaches (range, 39-53%). There was lower risk of sensitization to cockroach allergens for subjects <21 years old living in suburban (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.12-0.81) and rural environments (OR, 0.33; 95% CI, 0.11-0.96) compared with subjects <21 years old living in urban areas. There was higher risk of sensitization to fungi in subjects <21 years old living in suburban areas (OR, 1.51; 95% CI, 0.60-3.77) and rural environments (OR, 2.71; 95% CI, 0.98-7.48) compared with subjects <21 years old living in urban environments. CONCLUSION: Sensitization patterns are similar in different areas of residence except in younger subjects. Sensitization to fungi was higher in younger subjects from the rural area and cockroach sensitization were higher in younger subjects from urban areas. Sensitization is an important precursor of clinical allergic disease and further studies to unravel the complex gene-environment interactions of aeroallergen sensitization in different environments are needed.

Consumption of organic foods and risk of atopic disease during the first 2 years of life in the Netherlands.

We prospectively investigated whether organic food consumption by infants was associated with developing atopic manifestations in the first 2 years of life. The KOALA Birth Cohort Study in the Netherlands (n 2764) measured organic food consumption, eczema and wheeze in infants until age 2 years using repeated questionnaires. Diet was defined as conventional ( 90 % organic). Venous blood samples taken from 815 infants at 2 years of age were analysed for total and specific IgE. Multivariate logistic regression models were fitted to control for potential confounding factors. Eczema was present in 32 % of infants, recurrent wheeze in 11 % and prolonged wheezing in 5 %. At 2 years of age, 27 % of children were sensitised against at least one allergen. Of all the children, 10 % had consumed a moderately organic diet and 6 % a strictly organic diet. Consumption of organic dairy products was associated with lower eczema risk (OR 0.64 (95 % CI 0.44, 0.93)), but there was no association of organic meat, fruit, vegetables or eggs, or the proportion of organic products within the total diet with the development of eczema, wheeze or atopic sensitisation. Further studies to substantiate these results are warranted.

Breast-feeding duration and infant atopic manifestations, by maternal allergic status, in the first 2 years of life (KOALA study).

OBJECTIVE: To investigate the potential effect of modification by maternal allergic status on the relationship between breast-feeding duration and infant atopic manifestations in the first 2 years of life. STUDY DESIGN: Data from 2705 infants of the KOALA Birth Cohort Study (The Netherlands) were analyzed. The data were collected by repeated questionnaires at 34 weeks of gestation and 3, 7, 12, and 24 months postpartum. Total and specific immunoglobulin E measurements were performed on venous blood samples collected during home visits at age 2 years. Relationships were analyzed using logistic regression analyses. RESULTS: Longer duration of breast-feeding was associated with a lower risk for eczema in infants of mothers without allergy or asthma (P(trend) = .01) and slightly lower risk in those of mothers with allergy but no asthma (P(trend) = .14). There was no such association for asthmatic mothers (P(trend) = .87). Longer breast-feeding duration decreased the risk of recurrent wheeze independent of maternal allergy (P(trend) = .02) or asthma status (P(trend) = .06). CONCLUSIONS: Our findings show that the relationship between breast-feeding and infant eczema in the first 2 years of life is modified by maternal allergic status. The protective effect of breast-feeding on recurrent wheeze may be associated with protection against respiratory infections.

Influence of organic diet on the amount of conjugated linoleic acids in breast milk of lactating women in the Netherlands.

The aim of the present study was to find out whether the incorporation of organic dairy and meat products in the maternal diet affects the contents of the conjugated linoleic acid isomers (CLA) and trans-vaccenic acid (TVA) in human breast milk. To this purpose, milk samples from 312 breastfeeding mothers participating in the KOALA Birth Cohort Study have been analysed. The participants had documented varying lifestyles in relation to the use of conventional or organic products. Breast milk samples were collected 1 month postpartum and analysed for fatty acid composition. The content of rumenic acid (the main CLA) increased in a statistically significant way while going from a conventional diet (no organic dairy/meat products, 0.25 weight % (wt%), n 186) to a moderately organic diet (50-90 % organic dairy/meat, 0.29 wt%, n 33, P = 0.02) and to a strict organic diet (>90 % organic dairy/meat, 0.34 wt%, n 37, P

Diphtheria, pertussis, poliomyelitis, tetanus, and Haemophilus influenzae type b vaccinations and risk of eczema and recurrent wheeze in the first year of life: the KOALA Birth Cohort Study.

OBJECTIVES: Among potential etiologic factors for atopic manifestations, infant vaccinations have recently been discussed. We evaluated in a prospective design whether infants who were unvaccinated or vaccinated according to incomplete vaccination schedules in the first 6 months of age were at decreased risk for eczema and recurrent wheeze in the first year of life. METHODS: Information on vaccinations against diphtheria, pertussis, poliomyelitis, tetanus; Haemophilus influenzae type b vaccine; and eczema and recurrent wheeze was collected by repeated questionnaires in 2764 families participating in the KOALA Birth Cohort Study in The Netherlands. A standard vaccination schedule referred to 3 diphtheria, pertussis, poliomyelitis, tetanus, and Haemophilus influenzae type b vaccinations in the first 6 months with the first given in months 1 to 3; an incomplete vaccination schedule was defined as any other vaccination schedule. Exclusion criteria were prematurity (gestational age <37 weeks) and congenital abnormalities related to immunity (such as Down syndrome). Multiple logistic regression models were fitted to adjust for confounding factors. RESULTS: During the first year of life, the incidence of eczema was 23% (584 of 2537 infants) and of recurrent wheeze, the incidence was 8.5% (203 of 2402 infants). At age 6 months, 1969 (77%) of 2545 infants had been vaccinated according to a standard schedule, 393 (15%) vaccinated according to an incomplete schedule, and 182 (7%) never vaccinated. Compared with infants with standard vaccination schedules, infants with incomplete schedules did not differ significantly in eczema risk or recurrent wheeze. This was also true for infants who had never been vaccinated. CONCLUSION: This study shows that the risk of eczema or recurrent wheeze at 1 year of age does not differ between infants with different vaccination status at the age of 6 months.

Breastfeeding and infant eczema in the first year of life in the KOALA birth cohort study: a risk period-specific analysis.

OBJECTIVE: We studied the association between breastfeeding and eczema, taking into account the possible influence of reverse causation, with risk period-specific analyses. METHODS: Information on breastfeeding, determinants, and outcomes at 1 year of age was collected with repeated questionnaires for 2405 mother-infant pairs participating in the KOALA (Child, Parent and Health: Lifestyle and Genetic Constitution [in Dutch]) birth cohort study. By using multivariate logistic regression analysis, we compared an overall analysis with risk period-specific analyses. RESULTS: By the age of 1 year, 535 infants (22.2%) had developed eczema. In an overall analysis, we found a weak nonsignificant trend toward a reduced risk of eczema in the first year of life with increasing duration of breastfeeding (lowest risk for those breastfed for > or = 7 months versus never breastfed). In the risk period-specific analysis (confined to infants "at risk" for eczema onset after 3 months of age), no indication for reverse causation was found (results were not very different, compared with the overall analysis). Infants who were breastfed from birth on had a slightly (although not statistically significantly) increased risk for eczema in the first 3 months of life, compared with infants who were formula fed from birth on. CONCLUSIONS: Our results indicated that no strong effect of breastfeeding on eczema in the first year of life was present. This conclusion was strengthened by risk period-specific analysis, which made the influence of reverse causation unlikely.

Early life exposure to antibiotics and the subsequent development of eczema, wheeze, and allergic sensitization in the first 2 years of life: the KOALA Birth Cohort Study.

OBJECTIVES: Antibiotic exposure in early life may be associated with atopic disease development either by interfering with bacterial commensal flora or by modifying the course of bacterial infections. We evaluated early life exposure to antibiotics and the subsequent development of eczema, wheeze, and allergic sensitization in infancy. METHODS: Information on antibiotic use in the first 6 months and eczema and wheeze until age 2 was collected by repeated questionnaires in 2764 families participating in the KOALA (Child, Parent and Health: Lifestyle and Genetic Constitution [in Dutch]) Birth Cohort Study in The Netherlands. Antibiotic intake was evaluated both as maternal antibiotic use during breastfeeding and infant oral medication. Venous blood samples taken from 815 infants at 2 years of age were analyzed for total and specific immunoglobulin E against common food and inhalant allergens using a radioallergosorbent test. Multivariate logistic regression analysis was used to adjust for confounding factors. RESULTS: During the first 2 years, eczema was present in 32% of all infants, recurrent wheeze in 11%, and prolonged wheezing in 5%. At 2 years old, 27% of children were sensitized against > or = 1 allergen. At 6 months old, 11% had been exposed to antibiotics through breast milk and 20% directly through medication. The risk for recurrent wheeze, and prolonged wheeze was higher in infants directly exposed to antibiotics through medication, also after excluding from the analyses children who wheezed in the same period as an antibiotic had been used (avoiding reverse causation). Antibiotic use through breastfeeding was associated with recurrent wheeze, but prolonged wheeze was not. Eczema and sensitization were not associated with antibiotic exposure. CONCLUSIONS: We demonstrated that early antibiotic use preceded the manifestation of wheeze but not eczema or allergic sensitization during the first 2 years of life. Different biological mechanisms may underlie the etiology of wheeze compared with eczema or sensitization. Antibiotic exposure through breastfeeding enhanced the risk for recurrent wheeze, but this needs further confirmation.

Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study.

BACKGROUND AND AIMS: Perturbations in intestinal microbiota composition due to lifestyle changes may be involved in the development of atopic diseases. We examined gut microbiota composition in early infancy and the subsequent development of atopic manifestations and sensitisation. METHODS: The faeces of 957 infants aged 1 month and participating in the KOALA Birth Cohort Study were analysed using quantitative real-time PCR. Information on atopic symptoms (eczema, wheeze) and potential confounders was acquired through repeated questionnaires. Total and specific IgE were measured in venous blood samples collected during home visits when the infant was 2 years old. During these home visits a clinical diagnosis of atopic dermatitis was made according to the UK-Working Party criteria. RESULTS: The presence of Escherichia coli was associated with a higher risk of developing eczema (OR(adj) = 1.87; 95% CI 1.15 to 3.04), this risk being increased with increasing numbers of E coli (p(for trend) = 0.016). Infants colonised with Clostridium difficile were at higher risk of developing eczema (OR(adj) = 1.40; 95% CI 1.02 to 1.91), recurrent wheeze (OR(adj) = 1.75; 95% CI 1.09 to 2.80) and allergic sensitisation (OR(adj) = 1.54; 95% CI 1.02 to 2.31). Furthermore, the presence of C difficile was also associated with a higher risk of a diagnosis of atopic dermatitis during the home visit (OR(adj) = 1.73; 95% CI 1.08 to 2.78). CONCLUSION: This study demonstrates that differences in gut microbiota composition precede the development of atopy. Since E coli was only associated with eczema and C difficile was associated with all atopic outcomes, the underlying mechanisms explaining these association may be different.

Factors influencing the composition of the intestinal microbiota in early infancy.

OBJECTIVE: The aim of this study was to examine the contribution of a broad range of external influences to the gut microbiotic composition in early infancy. METHODS: Fecal samples from 1032 infants at 1 month of age, who were recruited from the KOALA Birth Cohort Study in the Netherlands, were subjected to quantitative real-time polymerase chain reaction assays for the enumeration of bifidobacteria, Escherichia coli, Clostridium difficile, Bacteroides fragilis group, lactobacilli, and total bacterial counts. Information on potential determinants of the gut microbiotic composition was collected with repeated questionnaires. The associations between these factors and the selected gut bacteria were analyzed with univariate and multivariate analyses. RESULTS: Infants born through cesarean section had lower numbers of bifidobacteria and Bacteroides, whereas they were more often colonized with C difficile, compared with vaginally born infants. Exclusively formula-fed infants were more often colonized with E coli, C difficile, Bacteroides, and lactobacilli, compared with breastfed infants. Hospitalization and prematurity were associated with higher prevalence and counts of C difficile. Antibiotic use by the infant was associated with decreased numbers of bifidobacteria and Bacteroides. Infants with older siblings had slightly higher numbers of bifidobacteria, compared with infants without siblings. CONCLUSIONS: The most important determinants of the gut microbiotic composition in infants were the mode of delivery, type of infant feeding, gestational age, infant hospitalization, and antibiotic use by the infant. Term infants who were born vaginally at home and were breastfed exclusively seemed to have the most "beneficial" gut microbiota (highest numbers of bifidobacteria and lowest numbers of C difficile and E coli).

Etiology of atopy in infancy: the KOALA Birth Cohort Study.

The aim of the KOALA Birth Cohort Study in the Netherlands is to identify factors that influence the clinical expression of atopic disease with a main focus on lifestyle (e.g., anthroposophy, vaccinations, antibiotics, dietary habits, breastfeeding and breast milk composition, intestinal microflora composition, infections during the first year of life, and gene-environment interaction). The recruitment of pregnant women started in October 2000. First, participants with 'conventional lifestyles' (n = 2343) were retrieved from an ongoing prospective cohort study (n = 7020) on pregnancy-related pelvic girdle pain. In addition, pregnant women (n = 491) with 'alternative lifestyles' with regard to child rearing practices, dietary habits (organic, vegetarian), vaccination schemes and/or use of antibiotics, were recruited through organic food shops, anthroposophic doctors and midwives, Steiner schools, and dedicated magazines. All participants were enrolled between 14 and 18 wk of gestation and completed an intake questionnaire on family history of atopy and infant care intentions. Documentation of other relevant variables started in the pregnant mother and covered the first and third trimester as well as early childhood by repeated questionnaires at 14-18, 30, and 34 wk of gestation and 3, 7, 12, and 24 months post-partum. A subgroup of participants, including both conventional and alternative lifestyles, was asked to consent to maternal blood sampling, breast milk and a faecal sample of the infant at 1 month post-partum, capillary blood at age 1 yr, venous blood and observation of manifestation of atopic dermatitis during home visits at the age of 2 yr (using the UK working party criteria and the severity scoring of atopic dermatitis index), and buccal swabs for DNA isolation from child-parent trios. From the start, ethical approval and informed consent procedures included gene-environment interaction studies. Follow-up at 3 and 7 months post-partum was completed with high response rates (respectively 90% and 88% in the conventional group, and 97% and 97% in the alternative group). The home visits at 2 yr of age will be completed in 2005. Preliminary results show that we have succeeded in recruiting a large population with various lifestyle choices with a fairly large contrast with regard to dietary habits (including organic foods, vegetarian diet), vaccination schemes and/or use of antibiotics. We have also been able to collect a large number of faecal samples (n = 1176) and capillary blood samples at age 1 yr (n = 956). Furthermore, a large proportion of the participants have consented with genetic studies. Mid 2006 we expect to report our first results on the relationship between the various exposures in early life and childhood atopy. An outline of the focus and design of the KOALA Birth Cohort Study is presented.