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Observational Study
. 2021 Sep;76(9):2855-2865.
doi: 10.1111/all.14857. Epub 2021 Jun 8.

Prevalence and early-life risk factors of school-age allergic multimorbidity: The EuroPrevall-iFAAM birth cohort

Sigurveig T Sigurdardottir  1   2 , Kristjan Jonasson  3 , Michael Clausen  4   5 , Kristin Lilja Bjornsdottir  6 , Sigridur Erla Sigurdardottir  5 , Graham Roberts  7   8   9 , Kate Grimshaw  10   11   12 , Nikolaos G Papadopoulos  13   14 , Paraskevi Xepapadaki  13 , Ana Fiandor  15 , Santiago Quirce  15 , Aline B Sprikkelman  16 , Lies Hulshof  17 , Marek L Kowalski  18 , Marcin Kurowski  18 , Ruta Dubakiene  19 , Odilija Rudzeviciene  20 , Johanna Bellach  21 , Songül Yürek  21 , Andreas Reich  22 , Sina Maria Erhard  23 , Philip Couch  24 , Montserrat Fernandez Rivas  25 , Ronald van Ree  26 , Clare Mills  27 , Linus Grabenhenrich  28 , Kirsten Beyer  21 , Thomas Keil  23   29   30
Affiliations
Observational Study

Prevalence and early-life risk factors of school-age allergic multimorbidity: The EuroPrevall-iFAAM birth cohort

Sigurveig T Sigurdardottir et al. Allergy. 2021 Sep.

Abstract

Background: Coexistence of childhood asthma, eczema and allergic rhinitis is higher than can be expected by chance, suggesting a common mechanism. Data on allergic multimorbidity from a pan-European, population-based birth cohort study have been lacking. This study compares the prevalence and early-life risk factors of these diseases in European primary school children.

Methods: In the prospective multicentre observational EuroPrevall-iFAAM birth cohort study, we used standardized questionnaires on sociodemographics, medical history, parental allergies and lifestyle, and environmental exposures at birth, 12 and 24 months. At primary school age, parents answered ISAAC-based questions on current asthma, rhinitis and eczema. Allergic multimorbidity was defined as the coexistence of at least two of these.

Results: From 10,563 children recruited at birth in 8 study centres, we included data from 5,572 children (mean age 8.2 years; 51.8% boys). Prevalence estimates were as follows: asthma, 8.1%; allergic rhinitis, 13.3%; and eczema, 12.0%. Allergic multimorbidity was seen in 7.0% of the whole cohort, ranging from 1.2% (Athens, Greece) to 10.9% (Madrid, Spain). Risk factors for allergic multimorbidity, identified with AICc, included family-allergy-score, odds ratio (OR) 1.50 (95% CI 1.32-1.70) per standard deviation; early-life allergy symptoms, OR 2.72 (2.34-3.16) for each symptom; and caesarean birth, OR 1.35 (1.04-1.76). Female gender, OR 0.72 (0.58-0.90); older siblings, OR 0.79 (0.63-0.99); and day care, OR 0.81 (0.63-1.06) were protective factors.

Conclusion: Allergic multimorbidity should be regarded as an important chronic childhood disease in Europe. Some of the associated early-life factors are modifiable and may be considered for prevention strategies.

Keywords: allergic multimorbidity; allergic rhinitis; asthma; children; eczema.

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Conflict of interest statement

Dr. Roberts reports grants from EU and grants from Food Standards Agency, during the conduct of the study; Dr. Grimshaw reports grants from Food Standards Agency UK, during the conduct of the study; Dr. Papadopoulos reports personal fees from Novartis, personal fees from Nutricia, personal fees from HAL, personal fees from MENARINI/FAES FARMA, personal fees from SANOFI, personal fees from MYLAN/MEDA, personal fees from BIOMAY, personal fees from AstraZeneca, personal fees from GSK, personal fees from MSD, personal fees from ASIT Biotech, personal fees from Boehringer Ingelheim, grants from Gerolymatos International SA and grants from Capricare, outside the submitted work; Dr. Xepapadaki reports personal fees from Uriach, personal fees from Novartis, personal fees from Nestle and personal fees from Nutricia, outside the submitted work; Dr. Fiandor reports personal fees and non‐financial support from AstraZeneca, outside the submitted work; Dr. Quirce reports personal fees and non‐financial support from GSK, personal fees and non‐financial support from AstraZeneca, personal fees and non‐financial support from Sanofi, personal fees and non‐financial support from Novartis, personal fees and non‐financial support from Mundipharma, personal fees and non‐financial support from Teva, and personal fees and non‐financial support from Allergy Therapeutics, outside the submitted work; Dr. Sprikkelman reports grants from Nutricia Advanced Medical Nutrition Netherlands, grants from AstraZeneca, Netherlands, grants from TEVA Netherlands and grants from GlaxoSmithKline Netherlands, during the conduct of the study, and grants from Aimmune, outside the submitted work; Dr. Couch reports grants from EU FP7‐KBBE, during the conduct of the study; Dr. Fernandez‐Rivas reports grants from European Commission, during the conduct of the study, personal fees from Aimmune, DBV, Novartis and SPRIM, and grants from Aimmune, Diater, ALK, DIATER, GSK and HAL Allergy, outside the submitted work; Dr. van Ree reports personal fees from HAL Allergy BV, personal fees from Citeq BV, personal fees from Angany Inc, personal fees from Thermo Fisher Scientific, grants from European Commission and grants from Dutch Science Foundation, outside the submitted work; ENC Mills reports grants from Reacta Biotech Ltd, outside the submitted work, and Chief Scientific Adviser and shareholder of Reacta Biotech Ltd, a start‐up developed to commercialise foods for use in oral food challenges; and Dr. Beyer reports grants from European Commission, during the conduct of the study, grants and personal fees from Aimmune, personal fees from Bencard, grants and personal fees from Danone/Nutricia/Milupa, grants and personal fees from DBV, grants and personal fees from Hipp, grants and personal fees from Hycor, grants and personal fees from InfectoPharm, personal fees from Jenapharm, personal fees from Mylan/Meda, personal fees from Nestle, personal fees from Novartis and personal fees from Thermo Fisher, outside the submitted work. All other authors have nothing to disclose.

Figures

FIGURE 1
FIGURE 1
Flow chart of the population‐based pan‐European birth cohort study showing the EuroPrevall and iFAAM participants up to inclusion in the current analysis. The EuroPrevall study centre Milan did not participate in the iFAAM project. The eight participating cities were as follows: Reykjavík, Iceland; Southampton, UK; Amsterdam, the Netherlands; Berlin, Germany; Lodz, Poland; Vilnius, Lithuania; Madrid, Spain; and Athens, Greece. ‘Not in current study’ are children whose parents were not reachable or were not interested in participation at school age
FIGURE 2
FIGURE 2
The eight centres of the population‐based EuroPrevall‐IFAAM birth cohort study, the number of children who participated in each one at the school‐age follow‐up assessment (in total 5572 children) and the proportion of these with allergic multimorbidity (overall proportion 7.0%)
FIGURE 3
FIGURE 3
Odds ratios and 95% confidence intervals for protective factors (green) and risk factors (red) of allergic multimorbidity at school age [of a model selected according to AICc]. Family‐allergy‐score is standardized to have SD = 1. Early‐age‐symptoms is in the range 1–3 and counts the number of allergic symptoms (of allergic rhinitis, eczema, asthma) observed before age 2. All the remaining variables are dichotomous. The OR for family‐allergy‐score shows the multiplicative effect for each standard deviation, and somewhat similarly, the OR for early‐age symptoms shows the multiplicative effect of each such symptom that is present. The factors shown are the ones present in a multivariate logistic model that maximizes the AICc model selection criterion
FIGURE 4
FIGURE 4
Odds ratios and 95% confidence intervals for covariates that are predictors for one or more of the individual diseases considered in the study (secondary outcomes). Covariates for which the confidence intervals do not contain 1 are coloured green if the factor is protective and red if it poses a risk. Confidence intervals of variables that are not selected into a corresponding model are shown in orange. See also explanations in the caption of Figure 3
See this image and copyright information in PMC

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