Hydrocortisone Dosing for Hypotension in Neonates: A Systematic Review & Meta-Analysis

Background Hypotension is common in neonates, particularly those who are preterm or very-low-birth-weight (VLBW) and is associated with poor outcomes, including brain injury and increased mortality. Relative adrenal insufficiency is a key contributor, with hydrocortisone (HC) often used to support cardiovascular stability. However, the optimal dosing strategy remains uncertain. Aim This meta-analysis evaluated the efficacy and safety of different hydrocortisone dosing regimens for treating hypotension in neonates including both preterm and term infants, focusing on blood pressure response, organ perfusion, and adverse effects. Methods Following PRISMA guidelines, randomized controlled trials (RCTs) published up to 2024 were systematically reviewed. RevMan 5.4 software was used for meta-analysis. Outcomes included improvement in blood pressure and perfusion, mortality, bronchopulmonary dysplasia (BPD), and adverse events such as hyperglycemia. Results Nine RCTs involving 2,044 neonates were included. Hydrocortisone (0.5 mg/kg every 6 hours to 5 mg/kg/day) significantly improved mean arterial pressure (mean increase: ~4 mmHg; OR = 0.43, 95% CI: 0.20–0.92, P = 0.03) and reduced inotrope requirements. HC reduced mortality prior to discharge (15.5% vs 23.7% in controls; OR = 0.08, 95% CI: 0.02–0.27, P < 0.0001) and lowered the incidence of BPD (OR = 0.32, 95% CI: 0.11–0.95, P = 0.04). However, treatment was associated with a higher risk of hyperglycemia (OR = 4.07, 95% CI: 1.04–15.90, P = 0.04). No consistent evidence was found for increased risk of gastrointestinal or neurosensory complications. Conclusion Hydrocortisone improves blood pressure, reduces inotrope use, and may lower mortality and BPD in both preterm and term neonates with hypotension. Lower-dose regimens appear effective with fewer metabolic complications, while higher doses increase hyperglycemia risk. Large, well-designed RCTs are still needed to define optimal dosing strategies.