Asthma and lower airway disease
Early-life determinants of asthma from birth to age 20 years: A German birth cohort study

https://doi.org/10.1016/j.jaci.2013.11.035Get rights and content

Background

The lack of longitudinal data analyses from birth to adulthood is hampering long-term asthma prevention strategies.

Objective

We aimed to determine early-life predictors of asthma incidence up to age 20 years in a birth cohort study by applying time-to-event analysis.

Methods

In 1990, the Multicenter Allergy Study included 1314 newborns in 5 German cities. Children were evaluated from birth to age 20 years at 19 time points. Using a Cox regression model, we examined the associations between 36 early-life factors and onset of asthma based on a doctor's diagnosis or asthma medication (primary outcome), typical asthma symptoms, or allergic asthma (including positive IgE measurements).

Results

Response at 20 years was 71.6%. Two hundred eighteen subjects met the primary outcome criteria within 16,257 person years observed. Asthma incidence was lower in participants who were vaccinated (measles, mumps, and rubella vaccine/tick-borne encephalitis vaccine/BCG vaccine: adjusted hazard ratio [HR], 0.66 [95% CI, 0.47-0.93]). Up to age 20 years, asthma incidence was higher in subjects who had parents with allergic rhinitis (adjusted HR, 2.24 [95% CI, 1.67-3.02]), started day care early or late (before 18 months: adjusted HR, 1.79 [95% CI, 1.03-3.10]; after 3 years: adjusted HR, 1.64 [95% CI, 0.96-2.79]), had mothers who smoked during pregnancy (adjusted HR, 1.79 [95% CI, 1.20-2.67]), had poor parents (adjusted HR, 1.55 [95% CI, 1.09-2.22]), and had parents with asthma (adjusted HR, 1.65 [95% CI, 1.17-2.31]). Not associated with asthma were aspects of diet and breast-feeding, pet ownership, presence of older siblings, and passive smoking.

Conclusion

Parental asthma and nasal allergy increase asthma incidence in offspring up to adulthood. Avoiding tobacco smoke exposure during pregnancy, receiving vaccinations in early childhood, and starting day care between 1.5 and 3 years of age might prevent or delay the development of asthma.

Section snippets

Study design, sampling, and follow-up

The German MAS-90 set out to trace the development and risk factors of allergic diseases prospectively from birth. Of 7609 children born between January and December 1990 in 6 obstetrics departments across Germany, a risk-enriched population-based sample was recruited (n = 1314) and followed up for 20 years: 38% with 2 or more first-degree allergic family members or increased cord blood IgE levels (≥0.9 kU/L) were considered at increased risk for allergies, whereas 62% were at low risk for

Study population

Of 1314 newborns recruited, 941 (71.6%) were followed up for 20 years. In total, 13.9% were lost during preschool age (until 6 years), and 6.5% were lost between 6 and 12 years of age (Fig 1). Median follow-up was 19.9 years (interquartile range, 15.0-20.2 years), with a total of 16,257 person years available for time-to-event analysis of the primary outcome, accounting for interval censoring.

Families with the lowest educational level were more likely to be lost during follow-up (followed vs

Key findings

Of a large number of perinatal and early-life factors that we evaluated, only a few showed associations with asthma up to age 20 years using time-to-event analysis on the German MAS-90 birth cohort data set. Asthma incidence was lower in participants who were vaccinated and higher in children of parents with allergic rhinitis, asthma, eczema, or increased cord blood IgE levels; who started day care before 18 months or after 3 years; who had mothers who smoked during pregnancy; and who had poor

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    The Multicenter Allergy Study (MAS) was funded by grants from the German Federal Ministry of Education and Research (07015633, 07 ALE 27, 01EE9405/5, and 01EE9406) and the German Research Foundation (KE 1462/2-1). This work was further supported by the Kompetenznetz Adipositas (Obesity Competence Network) funded by the German Federal Ministry of Education and Research (FKZ: 01GI1121A).

    Disclosure of potential conflict of interest: L. B. Grabenhenrich, A. Reich, N. Eckers, F. Zepp, D. Schramm, U. Hoffmann, J. Beschorner, P. Wagner, R. Bergmann, K. Bergmann, U. Wahn, and T. Keil have received research support from the German Federal Ministry of Education and Research, the German Research Foundation, and the Obesity Competence Network. H. Gough has received research support from the German Federal Ministry of Education and Research, the German Research Foundation, and the Obesity Competence Network and has received travel support from the European Academy of Allergology and Clinical Immunology. O. Nitsche has received research support from the German Federal Ministry of Education and Research, the German Research Foundation, and the Obesity Competence Network; has received payment for lectures from Allergopharma; and has received payment for manuscript preparation from Novartis; and has received travel support from Chiesi, Allergopharma, Abbott, Infectopharm, and Novartis. J. Forster has received research support from the German Federal Ministry of Education and Research, the German Research Foundation, and the Obesity Competence Network and has received payment for expert testimony from Infectopharm. A. Schuster has received research support from the German Federal Ministry of Education and Research, the German Research Foundation, and the Obesity Competence Network; has consultant arrangements from HAL Allergy/Leiden and ALK-Abelló; and has received payment for lectures from GlaxoSmithKline, Merck Sharp Dohme, Forest Labs, Roche, Novartis, ALK-Abelló, HAL Allergy, Grunenthal, Asche-Chiesi, and Thermo Fisher Scientific. C.-P. Bauer has received research support from the German Federal Ministry of Education and Research, the German Research Foundation, and the Obesity Competence Network and has received payment for lectures from Nestlé, Merck Sharp Dohme, and Medapharm. P. M. Matricardi has received research support from the German Federal Ministry of Education and Research, the German Research Foundation, the Obesity Competence Network, and Trial Form Support and has received payment for lectures from Allergopharma and Trial Form Support. S. Lau has received research support from the German Federal Ministry of Education and Research, the German Research Foundation, the Obesity Competence Network, Symbiopharm Herborn, Germany, and Allergopharma and has received payment for lectures from Symbiopharm and GlaxoSmithKline.

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