Abstract
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. To describe the use of corticosteroids in extremely preterm infants and evaluate the association with neurodevelopmental outcomes. 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. Cumulative dose of dexamethasone and duration of therapy for dexamethasone and prednisolone or methyl prednisolone were evaluated. 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. 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. 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.
Highlights
Bronchopulmonary dysplasia (BPD) is a common complication of prematurity, affecting 20% to 75% of infants born before gestational age (GA) 29 weeks.[1-3]
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 neonatal intensive care unit (NICU) stay, including 279 exposed to dexamethasone, 137 exposed to prednisolone or methylprednisolone, and 79 exposed to both
We developed 3 different models to estimate the parallel associations of steroid exposure using quartiles of length of exposure or total cumulative dose; model 1 was adjusted for treatment group and GA at birth in weeks; model 2 was adjusted for potential confounders, ie, being small for gestational age (SGA) and level of respiratory support at 14 days; model 3 was further adjusted for level of maternal education and in-hospital severe adverse events (SAEs) that are associated with outcomes to improve the accuracy of the estimated association of steroid exposure
Summary
Bronchopulmonary dysplasia (BPD) is a common complication of prematurity, affecting 20% to 75% of infants born before gestational age (GA) 29 weeks.[1-3]. Postnatal corticosteroids have been used to prevent and treat BPD for more than 50 years in multiple trials involving thousands of infants.[7-9]. Multiple small trials and meta-analyses have demonstrated that short courses of low-dose dexamethasone may be useful for earlier weaning and extubation of infants undergoing mechanical ventilation at highest risk of BPD.[8,9,12]. The administration of dexamethasone to prevent BPD, especially in the first week of life, has been associated with increased risk for adverse effects, including cognitive, speech, and learning impairments, as well as cerebral palsy (CP).[13-25]. Prednisolone and methylprednisolone are synthetic glucocorticoids with similar potency that are used interchangeably in practice to prevent or treat BPD. Their effectiveness has only been evaluated retrospectively.[31,32]
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