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

## TL;DR

The study found that infants of asthmatic mothers have different cord blood protein levels linked to lung function and asthma risk.

## Contribution

The study identifies specific cord blood proteins associated with respiratory outcomes in infants of asthmatic mothers.

## Key findings

- Infants of asthmatic mothers had lower MMP-9 and IFN-γ and higher p62 levels.
- MMP-9 levels were inversely linked to bronchiolitis hospitalization and asthma risk.
- p62 levels were inversely associated with minute ventilation.

## Abstract

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.

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.

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] p
adj = 0.009) and Interferon gamma (IFN‐γ, β −0.77 [−1.21; −0.32], p
adj = 0.009), and higher levels of p62 (β 1.15 [0.30; 2.00], p
adj = 0.030). p62 levels were inversely associated with minute ventilation (β −16.18 [−28.44; −3.91], p
adj = 0.032). Functional residual capacity values were inversely associated with both IFN‐γ (β −1.26, [−2.41; −0.11], p
adj = 0.063) and MMP‐9 levels (β −1.27, [−2.53; −0.01], p
adj = 0.063). MMP‐9 levels were inversely associated with both the risk of bronchiolitis hospitalization (odds ratio 0.47, [0.29; 0.77], p
adj = 0.004) and the risk of asthma (aOR 0.53, 95% CI, 0.32–0.86, p
adj = 0.033).

Protein levels differed between offspring of asthmatic and non‐asthmatic mothers. These markers were associated with postnatal lung function, bronchiolitis hospitalization, and asthma.

In the BILD and BLT cohorts, we compared cord blood proteins in infants of mothers with and without asthma during pregnancy. Groups showed different protein levels. These markers were associated with postnatal lung function, bronchiolitis hospitalization, and asthma. Additionally, p62 was inversely associated with minute ventilation, MMP‐9 inversely with FRC and bronchiolitis/asthma risk, while IFN‐γ and MMP‐9 was positively associated with lung clearance index, highlighting distinct protein–lung function and disease associations. Abbreviations: BILD, Basel‐Bern Infant Lung Development cohort; BLT, Breathing for Life cohort; FRC, functional residual capacity; IFN‐γ, interferon gamma; p62, ubiquitin‐binding protein sequestosome 1; MMP‐9, matrix metalloproteinase‐9.