Impact of Postnatal Corticosteroid Use on Neurodevelopment at 18 to 22 Months' Adjusted Age: Effects of Dose, Timing, and Risk of Bronchopulmonary Dysplasia in Extremely Low Birth Weight Infants
a Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio
b Department of Statistics, Research Triangle Institute, Research Triangle Park, North Carolina
c Department of Pediatrics, University of Rochester, Rochester, New York
d Department of Pediatrics, University of Texas Southwestern, Dallas, Texas
e Department of Pediatrics, Emory University, Atlanta, Georgia
f Department of Pediatrics, Wayne State University, Detroit, Michigan
g Department of Pediatrics, University of California, San Diego, California
h Department of Pediatrics, Stanford University, Palo Alto, California
i Department of Pediatrics, Indiana University, Indianapolis, Indiana
OBJECTIVE. Postnatal steroid use decreases lung inflammation but increases impairment. We hypothesized that increased dose is associated with increased neurodevelopmental impairment, lower postmenstrual age at exposure increases impairment, and risk of bronchopulmonary dysplasia modifies the effect of postnatal corticosteroid.
METHODS. Steroid dose and timing of exposure beyond 7 days was assessed among 2358 extremely low birth weight infants nested in a prospective trial, with 1667 (84%) survivors examined at 18 to 22 months' postmenstrual age. Logistic regression tested the relationship between impairment (Bayley Mental Developmental Index/Psychomotor Developmental Index of <70,> palsy, or sensory impairment), total dose (tertiles: <0.9, 0.9–1.9, and 1.9 mg/kg), and postmenstrual age at first dose. Separate logistic regression tested effect modification according to bronchopulmonary dysplasia severity (Romagnoli risk > 0.5 as high risk, n = 2336 (99%) for days of life 4–7).
RESULTS. Three hundred sixty-six (16%) neonates were steroid-treated (94% dexamethasone). Treated neonates were smaller and less mature; 72% of those treated were at high risk for bronchopulmonary dysplasia. Exposure was associated with neurodevelopmental impairment/death. Impairment increased with higher dose; 71% dead or impaired at highest dose tertile. Each 1 mg/kg dose was associated with a 2.0-point reduction on the Mental Developmental Index and a 40% risk increase for disabling cerebral palsy. Older age did not mitigate the harm. Treatment after 33 weeks' postmenstrual age was associated with greatest harm despite not receiving the highest dose. The relationship between steroid exposure and impairment was modified by the bronchopulmonary dysplasia risk, with those at highest risk experiencing less harm.CONCLUSIONS. Higher steroid dose was associated with increased neurodevelopmental impairment. There is no "safe" window for steroid use in extremely low birth weight infants. Neonates with low bronchopulmonary dysplasia risk should not be exposed. A randomized trial of steroid use in infants at highest risk is warranted.
**As published in the March 3, 2009 Journal of the American Academy of Pediatrics***