Related Experiment Video
Updated: Aug 1, 2026
Assessment and Evaluation of the High Risk Neonate: The NICU Network Neurobehavioral Scale
Published on: August 25, 2014
Dexamethasone, Prednisolone, and Methylprednisolone Use and 2-Year Neurodevelopmental Outcomes in Extremely Preterm
Mihai Puia-Dumitrescu1, Thomas R Wood1, Bryan A Comstock2
1Division of Neonatology, Department of Pediatrics, University of Washington, Seattle.
Insights
Prolonged use of dexamethasone in extremely preterm infants was linked to poorer neurodevelopmental outcomes at two years. This highlights the need for standardized corticosteroid treatment protocols in neonatal intensive care units.
Area of Science:
- Neonatal Medicine
- Developmental Pediatrics
- Pharmacology
Background:
- Corticosteroid use in extremely preterm infants to prevent bronchopulmonary dysplasia varies, with limited data on long-term neurodevelopmental effects.
- Understanding the impact of these treatments is crucial for optimizing infant care and outcomes.
Purpose of the Study:
- To examine the association between corticosteroid exposure in extremely preterm infants and their neurodevelopmental outcomes at two years of age.
- To describe current practices in corticosteroid administration for extremely preterm infants.
Main Methods:
- Secondary analysis of the Preterm Erythropoietin Neuroprotection (PENUT) trial data, including 828 infants born between 24 and 27 weeks gestational age.
- Neurodevelopmental outcomes assessed at corrected age 2 years using the Bayley Scales of Infant Development-Third Edition (BSID-III).
- Evaluated cumulative dose and duration of dexamethasone, prednisolone, or methylprednisolone therapy.
Main Results:
- 38% of infants received at least one corticosteroid; 312 infants were exposed.
- Longer duration of dexamethasone treatment (over 14 days) was associated with significantly lower motor and language scores on the BSID-III at 2 years.
- Exposed infants generally had lower birth weights and earlier gestational ages compared to non-exposed infants.
Conclusions:
- Extended exposure to dexamethasone in extremely preterm infants correlates with adverse neurodevelopmental outcomes.
- Further research and standardization of corticosteroid treatment protocols are recommended to improve clinical practice and study reproducibility.
Importance:
Practice variability exists in the use of corticosteroids to treat or prevent bronchopulmonary dysplasia in extremely preterm infants, but there is limited information on longer-term impacts.
Objective:
To describe the use of corticosteroids in extremely preterm infants and evaluate the association with neurodevelopmental outcomes.
Design, Setting, And Participants:
This cohort study was a secondary analysis of data from the Preterm Erythropoietin Neuroprotection (PENUT) randomized clinical trial, conducted at 19 participating sites and 30 neonatal intensive care units (NICUs) in the US. Inborn infants born between 24 0/7 and 27 6/7 weeks gestational age between December 2013 and September 2016 were included in analysis. Data analysis was conducted between February 2021 and January 2022.
Exposures:
Cumulative dose of dexamethasone and duration of therapy for dexamethasone and prednisolone or methyl prednisolone were evaluated.
Main Outcomes And Measures:
Demographic and clinical characteristics were described in infants who did or did not receive corticosteroids of interest and survived to discharge. Neurodevelopmental outcomes at 2 years of age were evaluated using the Bayley Scales of Infant Development-Third Edition (BSID-III) at corrected age 2 years.
Results:
A total of 828 extremely preterm infants (403 [49%] girls; median [IQR] gestational age, 26 [25-27] weeks) born at 19 sites who survived to discharge were included in this analysis, and 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. 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). The median (IQR) start day was 29 (20-44) days for dexamethasone and 53 (30-90) days for prednisolone or methylprednisolone. The median (IQR) total days of exposure was 10 (5-15) days for dexamethasone and 13 (6-25) days for prednisolone or methylprednisolone. The median (IQR) cumulative dose of dexamethasone was 1.3 (0.9-2.8) mg/kg. After adjusting for potential confounders, treatment with dexamethasone for longer than 14 days was associated with worse neurodevelopmental outcomes, with mean scores in BSID-III 7.4 (95% CI, -12.3 to -2.5) points lower in the motor domain (P = .003) and 5.8 (95% CI, -10.9 to -0.6) points lower in the language domain (P = .03), compared with unexposed infants.
Conclusions And Relevance:
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.
