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.
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, disabling cerebral 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.
Wilson-Costello
Deanne
D
Rainbow Babies and Children's Hospital, Division of Neonatology, 11100 Euclid Ave, Cleveland, OH 44106, USA.
Walsh
Michele C
MC
Langer
John C
JC
Guillet
Ronnie
R
Laptook
Abbot R
AR
Stoll
Barbara J
BJ
Shankaran
Seetha
S
Finer
Neil N
NN
Van Meurs
Krisa P
KP
Engle
William A
WA
Das
Abhik
A
D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001997:Bronchopulmonary Dysplasia / Q000401:mortality / Q000517:prevention & control*; D002547:Cerebral Palsy / Q000139:chemically induced* / Q000175:diagnosis / Q000401:mortality; D015331:Cohort Studies; D002658:Developmental Disabilities / Q000139:chemically induced* / Q000175:diagnosis / Q000401:mortality; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D005865:Gestational Age; D006801:Humans; D007223:Infant; D052577:Infant, Extremely Low Birth Weight; D007231:Infant, Newborn; D011446:Prospective Studies; D012678:Sensation Disorders / Q000139:chemically induced* / Q000175:diagnosis / Q000401:mortality; D015996:Survival Rate
D000893:Anti-Inflammatory Agents; D003907:Dexamethasone