Markers in Infants of Mothers With Asthma and Associations With Respiratory Outcomes.

Abstract

BACKGROUND In utero mechanisms related to oxidative stress response, inflammation, and extracellular matrix turnover may influence fetal lung development in the offspring of asthmatic mothers. Therefore, we aimed to determine whether levels of cord blood proteins differ between the offspring of asthmatic and nonasthmatic mothers. In addition, we aimed to examine if these proteins are associated with infant lung function, bronchiolitis hospitalization in infancy, and asthma at six years. METHODS We compared protein levels of infants (n = 715) from the Swiss Basel-Bern Infant Lung Development and the Australian Breathing for Life Trial birth cohorts using Tobit regression and network analyses. Using adjusted linear and logistic regression, we determined their association with postnatal infant lung function, bronchiolitis hospitalization in infancy, and asthma at six years. RESULTS Infants born to asthmatic mothers had lower levels of matrix metalloproteinase-9 (MMP-9, β-coefficient [β] -0.67, 95% confidence interval [-1.07; -0.27] padj = 0.009) and Interferon gamma (IFN-γ, β -0.77 [-1.21; -0.32], padj = 0.009), and higher levels of p62 (β 1.15 [0.30; 2.00], padj = 0.030). p62 levels were inversely associated with minute ventilation (β -16.18 [-28.44; -3.91], padj = 0.032). Functional residual capacity values were inversely associated with both IFN-γ (β -1.26, [-2.41; -0.11], padj = 0.063) and MMP-9 levels (β -1.27, [-2.53; -0.01], padj = 0.063). MMP-9 levels were inversely associated with both the risk of bronchiolitis hospitalization (odds ratio 0.47, [0.29; 0.77], padj = 0.004) and the risk of asthma (aOR 0.53, 95% CI, 0.32-0.86, padj = 0.033). CONCLUSIONS Protein levels differed between offspring of asthmatic and non-asthmatic mothers. These markers were associated with postnatal lung function, bronchiolitis hospitalization, and asthma.