Prophylactic hydrocortisone in extremely preterm infants and brain MRI abnormality

Objective: To determine whether early low-dose hydrocortisone treatment in extremely preterm infants is associated with brain damage assessed by MRI at term equivalent of age (TEA).

Patients and outcomes: This is a predefined secondary analysis of brain abnormalities, observed by MRI at TEA, of patients randomly assigned to receive either placebo or hydrocortisone in the PREMILOC trial. Outcomes were based on brain abnormalities graded according to Kidokoro scores.

Results: Among 412 survivors at TEA, 300 MRIs were performed and 295 were suitable for analysis. Kidokoro scoring was completed for 119/148 and 110/147 MRIs in the hydrocortisone and placebo groups, respectively. The distribution of the Kidokoro white matter (WM) subscore and other subscores was not significantly different between the two groups. There was, however, a significant association between a higher overall Kidokoro score and hydrocortisone treatment (5.84 (SD 3.51) for hydrocortisone and 4.98 (SD 2.52) for placebo; mean difference, 0.86; 95% CI 0.06 to 1.66; p=0.04). However, hydrocortisone was not statistically associated with moderate-to-severe brain lesions (Kidokoro overall score ≥6) in a multivariate logistic regression model accounting for potential confounding variables (adjusted OR (95% CI) 1.27 (0.75 to 2.14), p=0.38). Bronchopulmonary dysplasia at 36 weeks postmenstrual age significantly predicted both WM damage (adjusted OR (95% CI) 2.70 (1.03 to 7.14), p=0.04) and global brain damage (adjusted OR (95% CI) 2.18 (1.19 to 3.99), p=0.01).

Conclusions: Early hydrocortisone exposure in extremely preterm infants is not statistically associated with either WM brain damage or overall moderate-to-severe brain lesions when adjusted for other neonatal variables.

Trial registration number: EudraCT number 2007-002041-20, NCT00623740.