Late Breaking Abstract - Differences in remodelling and autophagy-related biomarkers at birth from offspring of asthmatic and healthy mothers are associated with subsequent infant lung function and bronchiolitis hospitalisation in infancy

<bold>Background:</bold> The mechanisms underlying deficits in lung function and respiratory morbidity in infants born to mothers with asthma in pregnancy may be related to differences in intrauterine environment. <bold>Aims:</bold> To compare levels of cord blood biomarkers between infants born to mothers with asthma in pregnancy (Breathing for Life Trial, BLT) and those born to non-asthmatic mothers (Basel-Bern Infant Lung Development (BILD) cohort), focussing on specific markers which are related to remodelling (MMP9, PDGFaa), inflammation (TNF-α, IFN-γ) and autophagy (p62, BECN1, SIRT1) but also have role in lung development in utero. <bold>Methods:</bold> Using multivariate regression analyses of biomarkers, we compared the association of these specific biomarkers with subsequent postnatal lung function at 4-6 weeks (tPTEF/tE% and lung volume FRC) and the prevalence of bronchiolitis hospitalisation in infancy. <bold>Results:</bold> Term infants born to asthmatic mothers (n=131 vs. n=614 non-asthmatic) had lower levels of MMP9 (β-coef -0.78, p<0.001), IFN-γ (β -0.71, p=0.002), BECN1 (β -0.17, p=0.006), SIRT1 (β -0.27, p=0.015) and higher levels of p62 (β 0.17, p=0.006). p62 levels were inversely associated with tPTEF/tE (β -1.63, p=0.043, (n=50 vs. n=447) whilst MMP9 (β -1.31, p=0.046), PDGFaa (β -1.19, p=0.016) and IFN-γ levels (β -1.52, p=0.026) with FRC. MMP9 (aRR 0.51, p=0.003) and p62 levels (aRR 1.56, p=0.017) were associated with bronchiolitis hospitalisation in the first year of life (n=24 cases vs. n=542). <bold>Conclusion:</bold> Supporting the hypothesis of impaired intrauterine environment in asthmatic mothers, remodelling and autophagy markers were altered in their offspring in comparison to infants of healthy mothers. These biomarkers were associated with postnatal lung function and bronchiolitis prevalence in infancy.