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

Area of Science:

• Neonatalogy
• Pediatric Pharmacology
• Developmental Pediatrics

Background:

• Extremely preterm infants (EPIs) often require postnatal corticosteroids for bronchopulmonary dysplasia (BPD).
• The long-term effects of cumulative dexamethasone dose (CDD) on EPIs remain a critical concern.
• Understanding dose-response relationships is vital for optimizing treatment strategies.

Purpose of the Study:

• To investigate the association between cumulative dexamethasone dose (CDD) and long-term neurodevelopmental and growth outcomes in extremely preterm infants (EPIs).
• To identify potential thresholds of CDD associated with adverse outcomes.

Main Methods:

• Retrospective review of medical records for 518 EPIs (gestational age <28 weeks) from 2013-2021.
• Infants categorized into five groups based on CDD: no corticosteroids, <2 mg/kg, 2-<4 mg/kg (reference), 4-<8 mg/kg, and ≥8 mg/kg.
• Long-term outcomes, including neurodevelopmental impairment (NDI) and catch-up growth, assessed at corrected age of 18-24 months.

Main Results:

• A cumulative dexamethasone dose (CDD) of ≥8 mg/kg was significantly associated with increased risks of NDI or death (aOR 3.550), NDI (aOR 3.479), and failure to achieve catch-up growth (aOR 4.077).
• No significant differences in NDI or catch-up growth were observed for CDD < 8 mg/kg compared to the reference group.
• The median CDD was 4.24 mg/kg, initiated at a median age of 10 days.

Conclusions:

• Cumulative dexamethasone doses ≥8 mg/kg are linked to significantly higher risks of adverse neurodevelopmental and growth outcomes in extremely preterm infants.
• Lower cumulative doses (<8 mg/kg) were not associated with increased risk, suggesting a potential benefit in managing severe BPD.
• These findings highlight the importance of dose optimization for corticosteroid therapy in critically ill preterm neonates.