TYPE OF INVESTIGATION: Prognosis; exploratory secondary analysis of an interventional randomized controlled trial. QUESTION: In extremely preterm infant (<28 weeks), is early low-dose hydrocortisone compared to placebo associated with neurodevelopmental impairment at 2 years of age? METHODS: Patients: Surviving infants enrolled in the PREMILOC trial conducted in France between 2008 and 2014. INTERVENTION: Double-blind, multicenter, randomized, placebo-controlled trial of infants born between 24 0/7 weeks and 27 6/7 weeks of gestation and before 24 h of postnatal age, assigned to receive either placebo or low-dose hydrocortisone (0.5 mg/kg twice per day for 7 days, followed by 0.5 mg/kg per day for 3 days). MAIN RESULTS: For the pre-specified exploratory outcome, the distribution of patients without neurodevelopmental impairment (73% in the hydrocortisone group vs. 70% in the placebo group), with mild neurodevelopmental impairment (20% in the hydrocortisone group vs. 18% in the placebo group), or with moderate to severe neurodevelopmental impairment (7% in the hydrocortisone group vs. 11% in the placebo group) was not found to be statistically significantly different between the two groups (p = 0.33). Qualitative assessment of patients using standardized neurological examination also was not statistically significantly different between groups (p = 0.87). STUDY CONCLUSION: In this follow-up study of premature infants who were randomly assigned at birth to receive low-dose hydrocortisone or placebo for 10 days, hydrocortisone treatment was not associated with any adverse effects on neurodevelopmental outcome at 22 months of corrected age.