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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

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 postnata...

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Published in:Pediatrics (Evanston) 2009-03, Vol.123 (3), p.e430-e437
Main Authors: Wilson-Costello, Deanne, Walsh, Michele C, Langer, John C, Guillet, Ronnie, Laptook, Abbot R, Stoll, Barbara J, Shankaran, Seetha, Finer, Neil N, Van Meurs, Krisa P, Engle, William A, Das, Abhik, Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
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cited_by cdi_FETCH-LOGICAL-c400t-a1452b8b6af77f4d5cad1ab28c439b45e0729dafb03181cf147bc6ee811710c73
cites cdi_FETCH-LOGICAL-c400t-a1452b8b6af77f4d5cad1ab28c439b45e0729dafb03181cf147bc6ee811710c73
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container_title Pediatrics (Evanston)
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creator Wilson-Costello, Deanne
Walsh, Michele C
Langer, John C
Guillet, Ronnie
Laptook, Abbot R
Stoll, Barbara J
Shankaran, Seetha
Finer, Neil N
Van Meurs, Krisa P
Engle, William A
Das, Abhik
Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
description 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. 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 0.5 as high risk, n = 2336 (99%) for days of life 4-7). 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. 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.
doi_str_mv 10.1542/peds.2008-1928
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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. 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 &lt;70, disabling cerebral palsy, or sensory impairment), total dose (tertiles: &lt;0.9, 0.9-1.9, and &gt;/=1.9 mg/kg), and postmenstrual age at first dose. Separate logistic regression tested effect modification according to bronchopulmonary dysplasia severity (Romagnoli risk &gt; 0.5 as high risk, n = 2336 (99%) for days of life 4-7). 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. Higher steroid dose was associated with increased neurodevelopmental impairment. There is no "safe" window for steroid use in extremely low birth weight infants. 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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. 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 &lt;70, disabling cerebral palsy, or sensory impairment), total dose (tertiles: &lt;0.9, 0.9-1.9, and &gt;/=1.9 mg/kg), and postmenstrual age at first dose. Separate logistic regression tested effect modification according to bronchopulmonary dysplasia severity (Romagnoli risk &gt; 0.5 as high risk, n = 2336 (99%) for days of life 4-7). 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. 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.</abstract><cop>United States</cop><pub>Am Acad Pediatrics</pub><pmid>19204058</pmid><doi>10.1542/peds.2008-1928</doi><oa>free_for_read</oa></addata></record>
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subjects Anti-Inflammatory Agents - administration & dosage
Anti-Inflammatory Agents - adverse effects
Birth weight
Bronchopulmonary Dysplasia - mortality
Bronchopulmonary Dysplasia - prevention & control
Cerebral palsy
Cerebral Palsy - chemically induced
Cerebral Palsy - diagnosis
Cerebral Palsy - mortality
Clinical trials
Cohort Studies
Developmental Disabilities - chemically induced
Developmental Disabilities - diagnosis
Developmental Disabilities - mortality
Dexamethasone - administration & dosage
Dexamethasone - adverse effects
Dose-Response Relationship, Drug
Follow-Up Studies
Gestational Age
Humans
Infant
Infant, Extremely Low Birth Weight
Infant, Newborn
Lung diseases
Motor ability
Pediatrics
Prospective Studies
Regression analysis
Sensation Disorders - chemically induced
Sensation Disorders - diagnosis
Sensation Disorders - mortality
Steroids
Survival Rate
title 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
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