Inhaled versus systemic corticosteroids for the treatment of chronic lung disease in ventilated very low birth weight preterm infants.
BACKGROUND
Chronic lung disease (CLD) remains a serious and common problem among very low birth weight infants despite the use of antenatal steroids and postnatal surfactant therapy to decrease the incidence and severity of respiratory distress syndrome. Corticosteroids have been widely used to treat or prevent CLD due to their anti-inflammatory properties. However, the use of systemic steroids has been associated with serious short and long term adverse effects. Administration of corticosteroids topically through the respiratory tract might result in beneficial effects on the pulmonary system with fewer undesirable systemic side effects.


OBJECTIVE
To compare the effectiveness of inhaled versus systemic corticosteroids administered to ventilator dependent preterm neonates with birth weight </= 1500 grams or gestational age </= 32 weeks after two weeks of life for the treatment of evolving CLD.


METHODS
Randomized and quasi-randomized trials were identified by searching the Cochrane Controlled Trials Register (The Cochrane Library, Issue 3, 2002), MEDLINE (1966 - September 2002), EMBASE (1980 - September 2002), CINAHL (1982 - September 2002), reference lists of published trials and abstracts published in Pediatric Research (1990 - April 2002) from the Society for Pediatric Research/Pediatric Academic Societies' Annual Meetings.


METHODS
Randomized or quasi-randomized trials comparing inhaled versus systemic corticosteroid therapy (irrespective of the dose and duration of therapy) starting after the first two weeks of life in ventilator dependent very low birth weight preterm neonates.


METHODS
Data were extracted regarding clinical outcomes including CLD at 28 days or 36 weeks corrected gestational age (CGA), mortality, combined outcome of death or CLD at 28 days or 36 weeks CGA, other pulmonary outcomes and adverse effects. All data were analyzed using RevMan 4.1. When appropriate, meta-analysis was performed using relative risk (RR), risk difference (RD), and weighted mean difference (WMD) along with their 95% confidence intervals (CI). If RD was statistically significant, number needed to treat (NNT) was calculated.


RESULTS
Five trials comparing inhaled versus systemic corticosteroids in the treatment of CLD were identified. Two trials were excluded as both included non ventilator dependent patients. One trial is awaiting assessment and clarification of published data. Two trials qualified for inclusion in this review. Halliday et al (Halliday 2001a) randomized infants < 72 hours, while Suchomski et al (Suchomski 2002) randomized at 12-21 days. Although the steroids were commenced after the first 2 weeks of life in both the trials, the outcomes were measured over different time periods, from the age at randomization in each trial, making it inappropriate to combine results. In neither trial was there a statistically significant difference between the groups in the incidence of CLD at 36 weeks CGA amongst all randomized infants. The estimates for the trial by Halliday et al (Halliday 2001a) were RR 1.10 (95% CI 0.82, 1.47), RD 0.03 (95% CI -0.08, 0.15); number of infants (n) = 292 and for the trial by Suchomski et al (Suchomski 2002) RR 0.90 (95% CI 0.79, 1.02), RD -0.10 (95% CI -0.22, 0.02; n = 78 ). There were no statistically significant differences between the groups in either trial for oxygen dependency at 28 days, death by 28 days or 36 weeks, the combined outcome of death or CLD by 28 days or 36 weeks CGA, duration of intubation, duration of oxygen dependence, or adverse effects. Information on the long term neurodevelopmental outcomes was not available.


CONCLUSIONS
This review found no evidence that inhaled corticosteroids confer net advantages over systemic corticosteroids in the management of ventilator dependent preterm infants. Neither inhaled steroids, nor systemic steroids, can be recommended as standard treatment for ventilated preterm infants. There was no evidence of difference in effectiveness or side-effect profiles for inhaled versus systemic steroids. A better delivery system guaranteeing selective delivery of inhaled steroids to the alveoli might result in beneficial clinical effects without increasing side-effects. To resolve this issue, studies are needed to identify the risk/benefit ratio of different delivery techniques and dosing schedules for the administration of these medications. The long term effects of inhaled steroids, with particular attention to neurodevelopmental outcome, should be addressed in future studies.
Shah
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Shared Program in Neonatal-Perinatal Medicine, Division of Neonatology, University of Toronto, 600, University Avenue, Room 775A, Toronto, Ontario, Canada, M5G 1X5. sshahdoc@hotmail.com
Ohlsson
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Halliday
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Shah
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D000280:Administration, Inhalation; D001507:Beclomethasone / Q000008:administration & dosage; D002908:Chronic Disease; D003907:Dexamethasone / Q000008:administration & dosage; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000188:drug therapy*; D019102:Infant, Very Low Birth Weight; D008171:Lung Diseases / Q000188:drug therapy*; D012121:Respiration, Artificial
D005938:Glucocorticoids; D003907:Dexamethasone; D001507:Beclomethasone