The association of infant urinary adrenal steroids with the risk of childhood asthma development.

BACKGROUND

Adrenal steroids play important roles in early-life development. However, our understanding of the effects of perinatal adrenal steroids on the development of childhood asthma is incomplete.

OBJECTIVE

To evaluate the associations between early-life adrenal steroid levels and childhood asthma.

METHODS

Participants included the Infant Susceptibility to Pulmonary Infections and Asthma following Respiratory Syncytial Virus Exposure birth cohort children with untargeted urinary metabolomics data measured during early infancy (n = 264) and nasal immune mediator data measured concurrently at age 2 to 6 months (n = 76). A total of 11 adrenal steroid compounds were identified using untargeted metabolomics and 6 asthma-relevant nasal immune mediators from multiplex assays were a priori selected. Current asthma at ages 5 and 6 years was ascertained using validated questionnaires. Associations were tested using logistic and linear regression with confounders adjustment.

RESULTS

Pregnenetriol disulfate (adjusted odds ratio [aOR] = 0.20, 95% CI = 0.06-0.68) and 3a,21-dihydroxy-5b-pregnane-11,20-dione-21-glucuronide (aOR = 0.34, 95% CI = 0.14-0.75) were inversely associated with childhood asthma at 5 and 6 years after multiple testing adjustment. There was a significant interaction effect of pregnanediol-3-glucuronide by biological sex assigned at birth (aOR = 0.11, 95% CI = 0.02-0.51, for those with female sex) on childhood asthma. Pregnenetriol disulfate was inversely associated with granulocyte-macrophage colony-stimulating factor (β = -0.45, q-value = 0.05). 3a,21-dihydroxy-5b-pregnane-11,20-dione 21-glucuronide was inversely associated with interleukin [IL]-4 (β = -0.29, q-value = 0.02), IL-5 (β = -0.35, q-value = 0.006), IL-13 (β = -0.26, q-value = 0.02), granulocyte-macrophage colony-stimulating factor (β = -0.35, q-value = 0.006), and fibroblast growth factor-β (β = -0.24, q-value = 0.01) after multiple testing adjustment.

CONCLUSION

The inverse association between adrenal steroids downstream of progesterone and 17-hydroxypregnenolone and the odds of childhood asthma and nasopharyngeal type 2 immune biomarkers suggest that increased early-life adrenal steroids may suppress type 2 inflammation and protect against the development of childhood asthma.