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

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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.

Section snippets

Data sources

European population–based birth and mother-child cohorts participated if they included children born between 1989 and 2011, had information available on at least gestational age and weight at birth and lung function measurements in childhood (until age 18 years), and were willing and able to exchange original data.4 We identified 50 European cohorts selected from existing collaborations on childhood health or asthma-related outcomes (www.chicosproject.eu, www.birthcohortsenrieco.net, //www.ga2len.org

Subjects' characteristics

Information about the main characteristics of the cohorts are given in Table I. Detailed information about determinants, outcomes, and covariates is given in Tables E1 to E5. Of all participants, 8.2% (n = 2053) were born preterm (<37 weeks of gestational age), and 4.8% (n = 1191) were born with a low birth weight (<2500 g). The mean age at which spirometric assessments were performed was 8.5 years (range, 3.9-19.1 years). The proportion of children aged 11 years or older was 11.9% (n = 2972).

Early growth measures and lung function outcomes

Discussion

In this meta-analysis of individual participant data of 24,938 children from 24 birth cohorts, we observed that lower gestational age, smaller size at birth, and greater infant weight gain were all associated with lower childhood FEV1. The positive associations of birth weight and infant weight gain with FVC were larger than the positive associations of birth weight and infant weight gain with FEV1. This combination resulted in associations of higher birth weight and infant weight gain with

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    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.

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