Early administration of inhaled corticosteroids for preventing chronic lung disease in ventilated very low birth weight preterm neonates.
BACKGROUND
Chronic lung disease remains a common complication amongst preterm infants. There is increasing evidence that inflammation play an important role in the pathogenesis of CLD. Due to their strong anti-inflammatory properties corticosteroids is an attractive intervention strategy. However, there are growing concerns regarding short and long term effects of systemic corticosteroids. Theoretically, administration of inhaled corticosteroids may allow for beneficial effects on the pulmonary system with a lower risk of undesirable systemic side effects.


OBJECTIVE
To determine the impact of inhaled corticosteroids administered to ventilated very low birth weight preterm neonates in the first two weeks of life for the prevention of chronic lung disease(CLD).


METHODS
Systematic search in accordance with Cochrane Neonatal Review Group. Randomized and quasi-randomized trials were identified by searching MEDLINE, Embase, CINAHL, the Cochrane Library, reference lists of published trials and abstracts published in Pediatric Research.


METHODS
Randomized controlled trials of inhaled corticosteroid therapy initiated within the first 2 weeks of life in ventilated preterm infants with birth weight 1500 grams or less were included in this review.


METHODS
Data regarding clinical outcomes including chronic lung disease at 28 days or 36 weeks corrected gestational age (CGA), mortality, combined outcome of death or CLD at 28 days of age and at 36 weeks CGA, the need for systemic corticosteroids, failure to extubate within 14 days and adverse effects of corticosteroids were evaluated. All data were analyzed using Revman 3.1. When possible, meta-analysis was performed using relative risk (RR), risk difference (RD), along with their 95% confidence intervals (CI). If RD was significant, number needed to treat (NNT) was calculated.


RESULTS
Eight trials assessing the impact of inhaled corticosteroid for the prevention of CLD were identified. The study by Kovacs 1998 was excluded as investigators evaluated the impact of a combination of systemic and inhaled corticosteroid for prevention of CLD. Seven trials qualified for inclusion in this review but data from two of these studies are awaiting assessment. Thus, the present review includes data analyses based on five qualifying trials. There was no statistically significant effect of inhaled steroids on CLD either at 28 days or at 36 weeks CGA, when analyzed either for all randomized infants or amongst survivors. No statistically significant differences were noted for mortality or for the combined outcome of mortality and CLD either at 28 days of age or at 36 weeks CGA. The meta-analysis supports a reduction in the need for systemic steroids, RR 0.78 (95% CI 0.62, 0.99), RD -0. 097 (95% CI -0.187, -0.008); however statistical heterogeneity was noted. The number needed to treat (NNT) to reduce the need for systemic steroid was 10 (95% CI 5.3, 125). There were no statistically significant differences in adverse events between groups.


CONCLUSIONS
There is no evidence from the trials reviewed that early administration (in the first 2 weeks of life) of inhaled steroids to ventilated preterm neonates was effective in reducing the incidence of CLD. There was a reduction in the need for systemic steroids. Although this difference was statistically significant, there was significant heterogeneity between studies and the upper limit of the 95% CI for this outcome was very close to no effect. Currently, use of inhaled steroids in this population cannot be recommended. Studies are needed to identify the risk/benefit ratio of different delivery techniques and dosing schedules for the administration of these medications. Studies need to address both the short-term and long-term benefits and adverse effects of inhaled steroids with particular attention to neurodevelopmental outcome.
Shah
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Department of Newborn and Developmental Paediatrics, Sunnybrook and Women's College Health Sciences Centre, 76 Grenville Street, Toronto, Ontario, Canada, M5S 1B2. michael.dunn@swchsc.on.ca
Ohlsson
A
A
Halliday
H L
HL
Dunn
M S
MS
D000280:Administration, Inhalation; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002908:Chronic Disease; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000517:prevention & control*; D019102:Infant, Very Low Birth Weight; D008171:Lung Diseases / Q000517:prevention & control*; D012121:Respiration, Artificial; D013256:Steroids; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D013256:Steroids