Early-life determinants of asthma from birth to age 20 years: A German birth cohort study
Article InfoFig 1
Study population sampling (upper part) and follow-up (lower part). *High-risk study population defined through a positive family history, increased cord IgE levels, or both.
Fig 2
Age at incidence by case definitions: primary outcome asthma (at least 2 of: physician's diagnosis, indicative symptom, or asthma drugs; open diamonds); secondary outcome asthma symptoms (at least 2 of: wheezing, shortness of breath, or dry cough; open squares); and secondary outcome allergic asthma (primary outcome asthma plus aeroallergen sensitization, open circles).
Fig 3
Influence of socioeconomic factors and heredity on asthma development in offspring. Raw (open diamonds) and adjusted (solid diamonds and error bars, exact numbers are shown at right) HRs for the primary outcome asthma (at least 2 of: physician's diagnosis, indicative symptom, or asthma drugs) and adjusted HRs for secondary outcomes asthma symptoms (squares: at least 2 of: symptoms of wheezing, shortness of breath, or dry cough) and allergic asthma (circles: primary outcome asthma plus aeroallergen sensitization). Details on model building, including adjustment and proportionality assessment, are in Table E1 . aHR, Adjusted HR; BMI, body mass index.
Fig 4
Onset of asthma (at least 2 of: physician's diagnosis, indicative symptom, or asthma drugs) stratified by parental history of allergic disease (asthma, allergic rhinitis, or eczema). Black step function depicts real data; bands and gray steps represent trajectory estimates and 95% CIs based on the Cox proportional model.
Fig 5
Onset of asthma (at least 2 of: physician's diagnosis, indicative symptom, or asthma drugs) stratified by wheezing within first 3 years. Black step function depicts real data; bands and gray steps represent trajectory estimates and 95% CIs based on the Cox proportional model.
Fig 6
Influence of pregnancy and environmental and behavioral factors in the first 3 years of life on asthma development. Raw (open diamonds) and adjusted (solid diamonds and error bars, exact numbers are shown at right) HRs for the primary outcome of asthma (2 of physician's diagnosis, indicative symptom, or asthma drugs) and adjusted HRs for secondary outcomes of asthma symptoms (squares: 2 of wheezing, shortness of breath, or dry cough) and allergic asthma (circles: based on physician's diagnosis and aeroallergen sensitization) are shown. Details on model building, including adjustment and proportionality assessment, are shown in Table E1 . aHR, Adjusted HR; APGAR, postnatal adaptation score; MMR, measles, mumps, and rubella vaccine; SDS, standard deviation score; TBE, tick-borne encephalitis vaccine.
Fig E1
Missingness patterns, distribution, and appropriate methodology. With all 19 time points accounted for, the overall number of participants was 1314.
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.
Key words:
Infant, child, preschool, adolescent, heredity, risk factors, epidemiologic factors, survival analysis, hypersensitivity, immunizationAbbreviations used:
HR (Hazard ratio), ISAAC (International Study of Asthma and Allergies in Childhood), MAS-90 (Multicenter Allergy Study)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.
