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: This study aimed to evaluate the associations between early life adrenal steroid levels and childhood asthma.

METHODS: Participants included INSPIRE birth cohort children with untargeted urinary metabolomics data measured during early infancy (n=264) and nasal immune mediator data measured concurrently at age 2-6 months (n=76). A total of 11 adrenal steroid compounds 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 odd 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 sex (aOR=0.11, 95%CI=[0.02, 0.51], for females) on childhood asthma. Pregnenetriol disulfate was inversely associated with GM-CSF (b=-0.45, q-value=0.05). 3a,21-dihydroxy-5b-pregnane-11,20-dione 21-glucuronide was inversely associated with IL-4 (b=-0.29, q-value=0.02), IL-5 (b=-0.35, q-value=0.006), IL-13 (b=-0.26, q-value=0.02), GM-CSF (b=-0.35, q-value=0.006), and FGF-b(b=-0.24, q-value=0.01) after multiple testing adjustment.

CONCLUSION: The inverse association between adrenal steroids downstream of progesterone and 17-hydroxypregnenolone and 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.