Threshold Effect of Cumulative Postnatal Corticosteroid Dose on Long-Term Outcomes in Extremely Preterm Infants

Background/Objectives: To evaluate the association between cumulative dexamethasone dose (CDD) and long-term outcomes in extremely preterm infants (EPIs, gestational age <28 weeks). Methods: We retrospectively reviewed the medical records of 518 EPIs admitted from 2013 to 2021. Infants were categorized by CDD into five groups: no corticosteroids, <2 mg/kg, 2-<4 mg/kg (reference), 4-<8 mg/kg, and ≥8 mg/kg. Outcomes were assessed at corrected age of 18-24 months, including neurodevelopmental impairment (NDI), and failure to achieve catch-up growth. Results: Of 518 infants, 91.7% received postnatal corticosteroids. The median CDD was 4.24 mg/kg, initiated at a median age of 10 days. Among the 400 survivors at a corrected age of 18-24 months, 386 were followed up to evaluate long-term outcomes. A CDD ≥ 8 mg/kg was significantly associated with higher risks of NDI or death (adjusted OR 3.550, 95% CI: 1.260-10.004), NDI (adjusted OR 3.479, 95% CI: 1.074-11.268), and failure to achieve catch-up growth (adjusted OR 4.077, 95% CI: 1.217-13.656), compared to the reference group. No significant differences in NDI or failure to achieve catch-up growth were found in groups with CDD < 8 mg/kg. Conclusions: CDD ≥ 8 mg/kg was associated with significantly increased risks of adverse neurodevelopmental and growth outcomes, even when initiated after a median age of 7 days. Lower cumulative doses were not associated with increased risk, suggesting that, in critically ill infants with severe bronchopulmonary dysplasia (BPD), such doses may help reduce BPD severity and BPD-related mortality.