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Early growth characteristics and the risk of reduced lung function and asthma: A meta-analysis of 25,000 children
Herman T den Dekker1, Agnes M M Sonnenschein-van der Voort1, Johan C de Jongste2
1Department of Pediatrics, Division of Respiratory Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands; Generation R Study Group, Erasmus University Medical Center, Rotterdam, The Netherlands.
Insights
Early life growth factors like preterm birth and low birth weight impact childhood asthma risk by affecting lung function. These factors are linked to reduced airway patency, explaining a significant portion of asthma development.
Area of Science:
- Pediatric respiratory health
- Developmental origins of health and disease
Background:
- Children born preterm or small for gestational age face higher risks of childhood asthma.
- Reduced airway patency is hypothesized to underlie these associations.
Purpose of the Study:
- To investigate the link between early growth characteristics and childhood lung function.
- To determine if reduced airway patency mediates the association between early growth and asthma risk.
Main Methods:
- Meta-analysis of individual participant data from 24,938 children across 24 birth cohorts.
- Examination of associations between gestational age, size for gestational age, infant weight gain, and childhood lung function (FEV1, FEV1/FVC, FEF75).
- Mediation analyses to assess the role of lung function in the early growth-asthma relationship.
Main Results:
- Younger gestational age and smaller size for gestational age were linked to lower FEV1 and altered FEV1/FVC ratios.
- Greater infant weight gain was associated with higher FEV1 but lower FEV1/FVC and FEF75.
- Preterm birth, low birth weight, and greater infant weight gain increased childhood asthma risk (ORs 1.34, 1.32, 1.27).
- Lung function parameters (FEV1, FEV1/FVC, FEF75) mediated 7-45% of the early growth-asthma associations.
Conclusions:
- Early growth characteristics, including gestational age and size for gestational age, significantly influence childhood lung function.
- These lung function changes substantially explain the increased risk of childhood asthma associated with adverse early growth.
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.
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