Limiting Neonatal Exposure to Dexamethasone in BPD minimizes Adverse Neurodevelopmental Outcome

Routine dexamethasone therapy in the first week of life is not recommended. Currently, most clinicians prescribe low-dose, late-initiated dexamethasone of shorter duration than what was previously used to maximize benefits and minimize potential risks. Their effectiveness has only been evaluated retrospectively and there is limited information on longer-term impacts. Therefore, Dr Mihai Puia-Dumitrescu and his team conducted a study to describe the use of corticosteroids in extremely preterm infants and evaluate the association with neurodevelopmental outcomes.

The researchers conducted a secondary analysis of data from the Preterm Erythropoietin Neuroprotection (PENUT) randomized clinical trial. They included 828 extremely preterm infants born at 19 sites who survived to discharge. They noted 312 infants (38%) were exposed to at least 1 corticosteroid of interest during their NICU stay, including 279 exposed to dexamethasone, 137 exposed to prednisolone or methylprednisolone, and 79 exposed to both. The researchers evaluated the demographic and clinical characteristics in infants who did or did not receive corticosteroids of interest and survived to discharge. They evaluated the neurodevelopmental outcomes at 2 years of age using the Bayley Scales of Infant Development–Third Edition (BSID-III) at corrected age 2 years.

Key findings of the study:

• Upon analysis, the researchers found that exposed infants, compared with nonexposed infants, had a lower birth weight (mean [SD], 718 [168] g vs 868 [180] g) and were born earlier (mean [SD] gestational age, 25 [1] weeks vs 26 [1] weeks).
• They noted that the median (IQR) start day was 29 (20-44) days for dexamethasone and 53 (30-90) days for prednisolone or methylprednisolone and the median (IQR) total days of exposure was 10 (5-15) days for dexamethasone and 13 (6-25) days for prednisolone or methylprednisolone with a median (IQR) cumulative dose of 1.3 (0.9-2.8) mg/kg dexamethasone.
• After adjusting for potential confounders, they found that the treatment with dexamethasone for longer than 14 days was associated with worse neurodevelopmental outcomes, with mean scores in BSID-III 7.4 points, lower in the motor domain points and language domain, compared with unexposed infants.

The authors concluded, "These findings suggest that long duration and higher cumulative dose of dexamethasone were associated with worse neurodevelopmental scores at corrected age 2 years. Potential unmeasured differences in the clinical conditions of exposed vs unexposed infants may contribute to these findings. Improved standardization of treatment and documentation of indications would facilitate replication studies."

For further information:

DOI: 10.1001/jamanetworkopen.2022.1947

Keywords:

Dexamethasone, prednisolone, methylprednisolone, extremely preterm infants, 2 years outcome, neurodevelopmental outcomes, PENUT Trial, Bayley Scales of Infant Development–Third Edition, Bronchopulmonary dysplasia, JAMA Network Open.