Early growth characteristics and the risk of reduced lung function and asthma: A meta-analysis of 25,000 children

Herman T. den Dekker, Agnes M. M. Sonnenschein-van der Voort, Johan C. de Jongste, Isabella Anessi-Maesano, S. Hasan Arshad, Henrique Barros, Caroline S. Beardsmore, Hans Bisgaard, Sofia Correia Phar, Leone Craig, Graham Devereux, C. Kors van der Ent, Ana Esplugues, Maria P. Fantini, Claudia Flexeder, Urs Frey, Francesco Forastiere, Ulrike Gehring, Davide Gori, Anne C. van der GugtenA. John Henderson, Barbara Heude, Jesús Ibarluzea, Hazel M. Inskip, Thomas Keil, Manolis Kogevinas, Eskil Kreiner-Møller, Claudia E. Kuehni, Susanne Lau, Erik Mélen, Monique Mommers, Eva Morales, John Penders, Katy C. Pike, Daniela Porta, Irwin K. Reiss, Graham Roberts, Anne Schmidt, Erica S. Schultz, Holger Schulz, Jordi Sunyer, Matias Torrent, Maria Vassilaki, Alet H. Wijga, Carlos Zabaleta, Vincent W. V. Jaddoe, Liesbeth Duijts*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

147 Citations (Scopus)
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Background: Children born preterm or with a small size for gestational age are at increased risk for childhood asthma. Objective: We sought to assess the hypothesis that these associations are explained by reduced airway patency. Methods: We used individual participant data of 24,938 children from 24 birth cohorts to examine and meta-analyze the associations of gestational age, size for gestational age, and infant weight gain with childhood lung function and asthma (age range, 3.9-19.1 years). Second, we explored whether these lung function outcomes mediated the associations of early growth characteristics with childhood asthma. Results: Children born with a younger gestational age had a lower FEV1, FEV1/forced vital capacity (FVC) ratio, and forced expiratory volume after exhaling 75% of vital capacity (FEF75), whereas those born with a smaller size for gestational age at birth had a lower FEV1 but higher FEV1/FVC ratio (P < .05). Greater infant weight gain was associated with higher FEV1 but lower FEV1/FVC ratio and FEF75 in childhood (P < .05). All associations were present across the full range and independent of other early-life growth characteristics. Preterm birth, low birth weight, and greater infant weight gain were associated with an increased risk of childhood asthma (pooled odds ratio, 1.34 [95% CI, 1.15-1.57], 1.32 [95% CI, 1.07-1.62], and 1.27 [95% CI, 1.21-1.34], respectively). Mediation analyses suggested that FEV1, FEV1/FVC ratio, and FEF75 might explain 7% (95% CI, 2% to 10%) to 45% (95% CI, 15% to 81%) of the associations between early growth characteristics and asthma. Conclusions: Younger gestational age, smaller size for gestational age, and greater infant weight gain were across the full ranges associated with childhood lung function. These associations explain the risk of childhood asthma to a substantial extent.

Original languageEnglish
Pages (from-to)1026-1035
Number of pages10
JournalJournal of Allergy and Clinical Immunology
Issue number4
Early online date11 Nov 2015
Publication statusPublished - Apr 2016

Bibliographical note

Disclosure of potential conflict of interest: I. Anessi-Maesano has received a grant from the FP7 MeDALL project (Mechanisms of the Development of ALLergy, FP7 no. 261357) and has board memberships with the European Respiratory Journal, Clinical and Experimental Allergy, the International Journal of Tuberculosis and Lung Disease, BMC Public Health, the European Respiratory Review, Multidisciplinary Respiratory Medicine, Therapeutic Advances in Respiratory Disease, Multidisciplinary Review Frontiers in Medicine, and La lettre du pneumologue. S. H. Arshad has received grants from the National Institutes of Health (NIH) and the Medical Research Council and has consultant arrangements with Merck & Co. U. Frey and A. Schmidt have received grants from the Swiss National Science Foundation. A. J. Henderson has received grants from the Medical Research Council and the Wellcome Trust. H. M. Inskip has received grants from the UK Medical Research Council, the British Heart Foundation, Asthma Research UK, the British Lung Foundation, the Food Standards Agency, and the Dunhill Medical Trust; is deputy chair of a grant-funding board for the UK Medical Research Council; and has her employment funded by the Medical Research Council. S. Lau has received grants from the German Research Foundation, Allergopharma, and Symbiopharma and has consultant arrangements with Merck. K. C. Pike has received grants from the Food Standards Agency and the British Lung Foundation. The rest of the authors declare that they have no relevant conflicts of interest.


  • asthma
  • children
  • infant growth
  • low birth weight
  • lung function
  • meta-analysis
  • preterm birth


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