Reduction In Chronic Lung Disease Research Articles

Non-invasive high-frequency ventilation in newborn infants with respiratory distress.

Non-invasive high-frequency ventilation in newborn infants with respiratory distress.

Bronchodilators for the prevention and treatment of chronic lung disease in preterm infants.

Chronic lung disease (CLD) occurs frequently in preterm infants. Bronchodilators have the potential effect of dilating small airways with muscle hypertrophy. Increased compliance and tidal volume and decreased pulmonary resistance have been documented with the use of bronchodilators in infants with CLD. Therefore, bronchodilators might have a role in the prevention and treatment of CLD. To determine the effect of bronchodilators given as prophylaxis or as treatment for CLD on mortality and other complications of preterm birth in infants at risk for or identified as having CLD. On 2016 March 7, we used the standard strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2), MEDLINE (from 1966), Embase (from 1980) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; from 1982). We searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We applied no language restrictions. Randomised and quasi-randomised controlled trials involving preterm infants were eligible for inclusion. Initiation of bronchodilator therapy for prevention of CLD had to occur within two weeks of birth. Treatment of patients with CLD had to be initiated before discharge from the neonatal unit. The intervention had to include administration of a bronchodilator by nebulisation, by metered dose inhaler (with or without a spacer device) or by intravenous or oral administration versus placebo or no intervention. Eligible studies had to include at least one of the following predefined clinical outcomes: mortality, CLD, number of days on oxygen, number of days on ventilator, patent ductus arteriosus (PDA), pulmonary interstitial emphysema (PIE), pneumothorax, intraventricular haemorrhage (IVH) of any grade, necrotising enterocolitis (NEC), sepsis and adverse effects of bronchodilators. We used the standard method described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). Two review authors extracted and assessed all data provided by each study. We reported risk ratio (RR), risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB) with 95% confidence interval (CI) for dichotomous outcomes and mean difference (MD) for continuous data. We assessed the quality of the evidence by using the GRADE approach. For this update, we identified one new randomised controlled trial investigating effects of bronchodilators in preterm infants. This study, which enrolled 73 infants but reported on 52 infants, examined prevention of CLD with the use of aminophylline. According to GRADE, the quality of the evidence was very low. One previously included study enrolled 173 infants to look at prevention of CLD with the use of salbutamol. According to GRADE, the quality of the evidence was moderate. We found no eligible trial that studied the use of bronchodilator therapy for treatment of individuals with CLD. Prophylaxis with salbutamol led to no statistically significant differences in mortality (RR 1.08, 95% CI 0.50 to 2.31; RD 0.01, 95% CI -0.09 to 0.11) nor in CLD (RR 1.03, 95% CI 0.78 to 1.37; RD 0.02, 95% CI -0.13 to 0.17). Results showed no statistically significant differences in other complications associated with CLD nor in preterm birth. Investigators in this study did not comment on side effects due to salbutamol. Prophylaxis with aminophylline led to a significant reduction in CLD at 28 days of life (RR 0.18, 95% CI 0.04 to 0.74; RD -0.35, 95% CI -0.56 to -0.13; NNTB 3, 95% CI 2 to 8) and no significant difference in mortality (RR 3.0, 95% CI 0.33 to 26.99; RD 0.08, 95% CI -0.07 to 0.22), along with a significantly shorter dependency on supplementary oxygen in the aminophylline group compared with the no treatment group (MD -17.75 days, 95% CI -27.56 to -7.94). Tests for heterogeneity were not applicable for any of the analyses, as each meta-analysis included only one study. Data are insufficient for reliable assessment of the use of salbutamol for prevention of CLD. One trial of poor quality reported a reduction in the incidence of CLD and shorter duration of supplementary oxygen with prophylactic aminophylline, but these results must be interpreted with caution. Additional clinical trials are necessary to assess the role of bronchodilator agents in prophylaxis or treatment of CLD. Researchers studying the effects of bronchodilators in preterm infants should include relevant clinical outcomes in addition to pulmonary mechanical outcomes. We identified no trials that studied the use of bronchodilator therapy for treatment of CLD.

Small Baby Unit Improves Quality and Outcomes in Extremely Low Birth Weight Infants

The survival rates for extremely low birth weight (ELBW) infants have improved, but many are discharged from the hospital with significant challenges. Our goal was to improve outcomes for this population by using a multidisciplinary team-based quality improvement approach. A unique program called the Small Baby Unit (SBU) was established in a children's hospital to care for the ELBW infant born at 28 weeks or less and weighing less than 1000 g at birth. These patients were cared for in a separate location from the main neonatal unit. A core multidisciplinary team that participates in ongoing educational and process-improvement collaboration provides care. Evidence-based guidelines and checklists standardized the approach. Data from the 2 years before and 4 years after opening the SBU are included. There was a reduction in chronic lung disease from 47.5% to 35.4% (P = .097). The rate of hospital-acquired infection decreased from 39.3% to 19.4% (P < .001). Infants being discharged with growth restriction (combined weight and head circumference <10th percentile) decreased from 62.3% to 37.3% (P = .001). Reduced resource utilization was demonstrated as the mean number per patient of laboratory tests decreased from 224 to 82 (P < .001) and radiographs decreased from 45 to 22 (P < .001). Care in a distinct unit by a consistent multidisciplinary SBU team using quality improvement methods improved outcomes in ELBW infants. Ongoing team engagement and development are required to sustain improved outcomes.

State of the art in conventional mechanical ventilation

Despite a shift to noninvasive respiratory support, mechanical ventilation remains an essential tool in the care of critically ill neonates. The availability of a variety of technologically advanced devices with a host of available modes and confusing terminology presents a daunting challenge to the practicing neonatologist. Many of the available modes have not been adequately evaluated in newborn infants and there is paucity of information on the relative merits of those modes that have been studied. This review examines the special challenges of ventilating the extremely low birth weight infants that now constitute an increasing proportion of ventilated infants, attempts to provide a simple functional classification of ventilator modes and addresses the key aspects of synchronized ventilation modes. The rationale for volume-targeted ventilation is presented, the available modes are described and the importance of the open-lung strategy is emphasized. The available literature on volume-targeted modalities is reviewed in detail and general recommendations for their clinical application are provided. Volume guarantee has been studied most extensively and shown to reduce excessively large tidal volumes, decrease incidence of inadvertent hyperventilation, reduce duration of mechanical ventilation and reduce pro-inflammatory cytokines. It remains to be seen whether the demonstrated short-term benefits translate into significant reduction in chronic lung disease. Avoidance of mechanical ventilation by means of early continuous positive airway pressure with or without surfactant administration may still be the most effective way to reduce the risk of lung injury. For babies who do require mechanical ventilation, the combination of volume-targeted ventilation, combined with the open-lung strategy appears to offer the best chance of reducing the risk of bronchopulmonary dysplasia.

Cochrane review: Elective high frequency oscillatory ventilation versus conventional ventilation for acute pulmonary dysfunction in preterm infants

AbstractBackgroundRespiratory failure due to lung immaturity is a major cause of mortality in preterm infants. Although the use of intermittent positive pressure ventilation (IPPV) in neonates with respiratory failure saves lives, its use is associated with lung injury and chronic lung disease (CLD). Conventional IPPV is provided at 30‐80 breaths per minute, while a newer form of ventilation called high frequency oscillatory ventilation (HFOV) provides 'breaths' at 10 ‐ 15 cycles per second. This has been shown to result in less lung injury in experimental studies.ObjectivesThe objective of this review is to determine the effect of the elective use of high frequency oscillatory ventilation (HFOV) as compared to conventional ventilation (CV) in preterm infants who are mechanically ventilated for respiratory distress syndrome (RDS), on the incidence of chronic lung disease, mortality and other complications associated with prematurity and assisted ventilation.Search strategySearches were made of the Oxford Database of Perinatal Trials, MEDLINE, EMBASE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal hand searching by the Cochrane Collaboration, mainly in the English language. The search was updated in April 2007.Selection criteriaRandomised controlled trials comparing HFOV and CV in preterm or low birth weight infants with pulmonary dysfunction, mainly due to RDS, who were given IPPV. Randomisation and commencement of treatment needed to be as soon as possible after the start of IPPV and usually in the first 12 hours of life.Data collection and analysisThe methodological quality of each trial was independently reviewed by the various authors. The standard effect measures are relative risk (RR) and risk difference (RD). From 1/RD the number needed to treat (NNT) to produce one outcome were calculated. For all measures of effect, 95% confidence intervals were used. In subgroup analyses the 99% CIs are also given for summary RRs in the text. Meta‐analysis was performed using a fixed effects model. Where heterogeneity was over 50%, the random effects RR is also given.Main resultsFifteen eligible studies of 3,585 infants were included. Meta‐analysis comparing HFOV with CV revealed no evidence of effect on mortality at 28 ‐ 30 days of age or at approximately term equivalent age. These results were consistent across studies and in subgroup analyses. The effect of HFOV on CLD in survivors at term equivalent gestational age was inconsistent across studies and the reduction was of borderline significance overall. Subgroups of trials showed a significant reduction in CLD with HFOV when high volume strategy for HFOV was used, when piston oscillators were used for HFOV, when lung protective strategies for CV were not used, when randomisation occurred at two to six hours of age, and when inspiratory:expiratory ratio of 1:2 was used for HFOV. In the meta‐analysis of all trials, pulmonary air leaks occurred more frequently in the HFOV group.In some studies, short‐term neurological morbidity with HFOV was found, but this effect was not statistically significant overall. The subgroup of two trials not using a high volume strategy with HFOV found increased rates of Grade 3 or 4 intraventricular haemorrhage and of periventricular leukomalacia. An adverse effect of HFOV on long‐term neurodevelopment was found in one large trial but not in the five other trials that reported this outcome. The rate of retinopathy of prematurity is reduced overall in the HFOV group.Authors' conclusionsThere is no clear evidence that elective HFOV offers important advantages over CV when used as the initial ventilation strategy to treat preterm infants with acute pulmonary dysfunction. There may be a small reduction in the rate of CLD with HFOV use, but the evidence is weakened by the inconsistency of this effect across trials and the overall borderline significance. Future trials on elective HFOV should target those infants who are at most risk of CLD (extremely preterm infants), compare different strategies for generating HFOV and CV, and report important long‐term neurodevelopmental outcomes.Plain language summaryInsufficient evidence exists to support the routine use of high frequency oscillatory ventilation (HFOV) instead of conventional ventilation for preterm infants with lung disease who are given positive pressure ventilation.High frequency oscillatory ventilation is a way of providing artificial ventilation of the lungs that theoretically may produce less injury to the lungs and therefore reduce the rate of chronic lung disease. This review of the evidence from fifteen randomised controlled trials showed variable results between studies and no clear overall benefit or harm resulting from HFOV.

Antenatal Glucocorticoid Treatment Decreases Mortality and Chronic Lung Disease in Survivors among 23- to 28-Week Gestational Age Preterm Infants

The purpose of this study was to analyze the influence of antenatal glucocorticoid therapy (AGT) on mortality and chronic lung disease (CLD) in surviving preterm infants 23 to 28 weeks gestational age (WGA). This was a multicenter, prospective, observational study. A total of 2448 infants 23 to 28 WGA were born in 2002 to 2003; 27.7% did not receive AGT, 18.8% were exposed to partial AGT, and 53.5% were exposed to complete AGT. A total of 883 died and 22.9% of 1537 survivors were affected by CLD. Unadjusted univariate analysis showed AGT was associated with a reduction in mortality (p<0.001), either with partial or complete AGT courses, and also with a reduction in CLD in survivors (p<0.001), but only with complete AGT courses. In logistic regression analysis adjusted for confounding factors and a propensity score for AGT, AGT was significant and independently associated with a reduction of mortality, but only for complete AGT course (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.47 to 0.87; p=0.004), and with a decrease in CLD if a complete AGT course was administered (OR, 0.63; 95% CI, 0.45 to 0.89; p=0.009). A complete course of AGT in 23 to 28 WGA pregnancies is associated with decreased rates of neonatal mortality and CLD disease in surviving infants.

Follow-up at 15 Years of Preterm Infants From a Controlled Trial of Moderately Early Dexamethasone for the Prevention of Chronic Lung Disease

Postnatal dexamethasone treatment of ventilator-dependent preterm infants results in rapid improvement in lung function and reduction in chronic lung disease. However, limited data are available on long-term outcomes after such therapy. We studied growth, neurodevelopmental, and pulmonary outcomes at adolescence in children who had participated in a double-blind, placebo-controlled trial of dexamethasone beginning at 2 weeks of age for the prevention of chronic lung disease. Thirty-six infants (birth weight < or =1250 g and gestational age < or =30 weeks) who were dependent on mechanical ventilation at 2 weeks of age received a 42-day course of dexamethasone, an 18-day course of dexamethasone, or saline placebo. Twenty-two children survived to 15 years (69% of the 42-day dexamethasone group, 67% of the 18-day dexamethasone group and 45% of the control group), and all were evaluated. Intact survival was defined as survival with normal neurologic examination, IQ >70, and receiving education in the regular classroom. There were no differences among groups for growth or incidence of neurologic abnormalities. The mean IQ for the 42-day dexamethasone group was 85 +/- 10 compared with 60 +/- 20 for the 18-day dexamethasone group and 73 +/- 23 for the control group. All children in the 42-day dexamethasone group were receiving education in the regular classroom compared with only 50% of the 18-day dexamethasone group and 40% of the control group. As a result, intact survival was significantly greater for the 42-day dexamethasone group (69%) than for either the 18-day dexamethasone group (25%) or the control group (18%). Pulmonary function was significantly better for the 42-day dexamethasone group compared with the 18-day dexamethasone group (eg, forced expiratory volume in 1 second: 90 +/- 16 vs 71 +/- 15% predicted, respectively). A 42-day course of dexamethasone therapy beginning at 2 weeks of age in preterm infants who are at high risk for severe chronic lung disease was associated with improved long-term neurodevelopmental outcome. Although additional research is needed to establish the optimal steroid preparation, dosage, and duration of therapy, these data support the view that moderately early (beginning at 1-2 weeks) corticosteroid treatment is advantageous for a select group of ventilator-dependent preterm infants.

Modeling and Remodeling of the Lung in Neonatal Chronic Lung Disease

Neonatal chronic lung disease (CLD) is the major long-term pulmonary complication of preterm birth affecting about 20% of infants who need mechanical ventilation. CLD is the result of abnormal repair processes following inflammatory lung injury that lead to remodeling of the lung. Inflammation may be initiated by a variety of stimuli including mechanical ventilation, oxygen toxicity and infection. The resultant neutrophil chemotaxis and degranulation leads to the release of enzymes such as matrix metalloproteinases that can cause proteolysis of the lung extracellular matrix. Abnormal healing with remodeling leads to poorly compliant lungs with reduced capacity for gas exchange. Drugs can influence the normal process of lung modeling or remodeling. Fetal lung development can be influenced by glucocorticosteroids and inflammation. Both can cause abnormal lung modeling with fewer, larger alveoli and accelerated lung maturation, which confers benefits in terms of reduced morbidity and mortality from respiratory distress syndrome but potentially increases the risk of subsequent lung injury. Antioxidants, such as retinol (vitamin A), administered post-natally may reduce the effects of oxidative stress leading to a modest reduction in CLD but they require repeated intramuscular injections. Postnatal glucocorticosteroid therapy can modify the lung inflammatory response and reduce CLD but it can also have detrimental effects on the developing brain and lung, thereby creating a clinical dilemma for neonatologists. Proteinase inhibitors may be a rational therapy but more research is needed before they can be accepted as a treatment for preterm neonates.'Modeling' is defined as planning or forming that follows a set pattern. The term is used to describe the normal process of lung growth and development that culminates in mature branching alveolar air spaces surrounded by a network of capillaries. Normal lung modeling occurs under a variety of genetic and hormonal influences that can be altered, leading to abnormal patterns of growth. 'Remodeling' is defined as altering the structure of or re-making and, in the case of the lung, is used to describe the abnormal patterns of lung growth that occur after lung injury. Modeling and remodeling of the lungs occur to an extent throughout life but never more rapidly than during the fetal and early neonatal periods, and factors that influence this process may lead to development of neonatal CLD. Some of the factors involved in normal and abnormal lung modeling and inflammation and glucocorticosteroid-induced remodeling in the perinatal period, in the context of neonatal CLD, are reviewed with considerations of how various drugs may influence these processes.

Replacement of estrogens and progestins to prevent morbidity and mortality in preterm infants

A potential therapeutic effect of sex steroids on premature infants has been proposed from animal data and observational studies in humans. Purported benefits include reduction in chronic lung disease, improved bone density and improved neurodevelopmental outcome. To determine if estrogens or progestins, either alone or in combination, when compared to placebo or no treatment, reduce morbidity and/or mortality in preterm infants. The standard search strategy of the Cochrane Neonatal Review Group as outlined in the Cochrane Library (Issue 2, 2004) was used. This included searches of the Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2004), MEDLINE 1966 to July 2004 inclusive, previous reviews including cross references, abstracts, conferences and symposia proceedings (Perinatal Society of Australia and New Zealand 1998-2004 and Pediatric Academic Societies meetings 1998-2004). Randomised controlled trials comparing the use of estrogens and/or progestins with placebo or no treatment in preterm infants born less than 30 weeks gestation were included in this review. The primary outcome measures were neonatal mortality and medium-term neurodevelopmental outcome. Other outcomes included length of hospital stay, incidence of chronic lung disease, osteopaenia causing fractures and adverse effects of sex steroid administration. Two reviewers independently selected, assessed the quality of and extracted data from the included studies. Meta-analyses were performed using relative risk and risk difference for dichotomous data, and weighted mean difference for continuous data with 95% confidence intervals. Two randomised controlled trials were identified by the search strategy and one was included in this review, comprising 30 preterm infants. There was no significant effect of replacement of estradiol and progesterone on the outcomes of mortality or neurodevelopmental disability in survivors followed. No adverse effects of sex steroid replacement on short or longer term outcomes were detected. The one small randomised controlled trial demonstrated neither evidence of benefit or harm related to the replacement of estradiol and progesterone in preterm infants less than 30 weeks gestation. A properly powered randomised controlled trial is required to determine whether or not administration of estradiol or progesterone, either alone or in combination, and at varying doses, confers any clinically significant benefits, or poses any risk, to the preterm infant.

5 A Randomized Prospective Comparative Trial of Elective Early High Frequency Oscillatory Ventilation (HFOV) in Preterm Infants with Respiratory Distress Syndrome (RDS)

Background: Chronic lung disease (CLD) is a major clinical problem in very low birth weight infants. It has been reported that by combining early use of HFOV (at high lung volumes) with exogenous surfactant, a further reduction in CLD could be achieved. Aim: the aim of this study was to examine the effect of applying an elective early HFOV at birth combined with surfactant treatment on improving the severity and rate of chronic lung disease.Methods: Preterm infants enrolled in this study were with gestational age of 32 weeks and birth weight of 2000 grams or less who required mechanical ventilation soon after birth and surfactant therapy to treat surfactant deficient respiratory distress syndrome (RDS). They were randomized into 2 groups, synchronized intermittent mechanical ventilation (SIMV) and HFOV. Infants, who had lethal anomalies, congenital infection or received conventional ventilation for more than 2 hours prior to enrollment, were excluded from the study. The study was conducted between August 2002 and December 2003. Data included were demographic data, complications of prematurity (CLD at 28 days and 36 weeks corrected age, PIE, PVL, IVH, ROP, NEC, PDA), days of ventilation and oxygenation, mode of delivery, antenatal steroids, PROM, failure of mechanical ventilation, sepsis, maternal age and death.Results: The two groups of patients (SIMV, N=29 & HFOV, N=32) were similar in demographic distribution of birth weight (959.55 ± 379.65, 906 ± 248.30), gestational age (27.58 ± 2.78,, 27.25 ± 1.95) and gender (M=17, F=12, M=20, F=12), and mode of delivery, antenatal steroids, Apgar score, sepsis, PIE, pneumothorax, IVH, PVL, NEC, PDA and ROP. There were significant statistical differences in days of ventilation between the two groups (SIMV=11.140± 16.56, HFOV=3.79± 5.91, P = 0.001) and in failure of SIMV, P= 0.047. There were no significant statistical differences between the 2 groups in terms of CLD at 28 days and 36 weeks corrected age, P = 0.372, 0.919 and in mortality rate.Conclusion: The elective early use of HFOV at birth did not improve the severity and rate of chronic lung disease. However, there was significant reduction in days of HFOV in comparison to SIMV.

Elective high frequency oscillatory ventilation versus conventional ventilation for acute pulmonary dysfunction in preterm infants.

Respiratory failure due to lung immaturity is a major cause of mortality in preterm infants. Although intermittent positive pressure ventilation (IPPV) saves lives, lung distortion during its use is associated with lung injury and chronic lung disease (CLD). Conventional IPPV is provided at 30-80 breaths per minute while a newer form of ventilation called high frequency oscillatory ventilation (HFOV) provides 'breaths' at 10-15 seconds. This has been shown to result in less lung injury in experimental studies. The objective of this review is to determine whether the elective use of high frequency oscillatory ventilation (HFOV) as compared to conventional ventilation in preterm infants who are mechanically ventilated for the respiratory distress syndrome decreases the incidence of chronic lung disease (CLD) without adverse effects. Searches were made of the Oxford Database of Perinatal Trials, MEDLINE, EMBASE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal handsearching by the Cochrane Collaboration, mainly in the English language. Expert informant's search in the Japanese language was made by Prof. Y. Ogawa. Randomized controlled trials comparing HFOV and CV in preterm or low birth weight infants with pulmonary dysfunction, mainly due to RDS, who are to be given IPPV. Randomization and commencement of treatment should have been as soon as possible after the start of IPPV and usually in the first 12 hours of life. The methodological quality of each trial was independently reviewed by the various authors. Each author extracted data separately; they were compared and differences were resolved. The standard method of the Cochrane Neonatal Review Group was used to synthesize the data using relative risk (RR) and risk difference (RD). From 1/RD the number needed to treat (NNT) for benefits, and number needed to harm (NNH) for adverse effects, were calculated. Meta-analysis of the six eligible studies comparing HFOV with CV revealed that there is no difference in mortality. There are trends toward decreases in CLD in survivors at 28-30 days, 'death or CLD at 28-30 days' and CLD in survivors at 36-37 weeks postmenstrual age or discharge in the HFOV group. However, there are trends towards increases in severe (grades 3 & 4) intraventricular hemorrhage (IVH) and in periventricular leukomalacia (PVL) in the HFOV group. HFOV results in a small increase in any air leak syndrome (ALS), [summary RR 1.20 (1.03, 1.39)]. Only 2 trials have included neurodevelopmental follow up and more survivors in the HFOV group are abnormal [summary RR 1.26 (1.01, 1.58)]. In the subgroup of four trials where a high volume strategy (HVS) was used, HFOV results in more favourable pulmonary outcomes. There are significantly lower rates of CLD in survivors at 28-30 days [summary RR 0.53 (0.36, 0.76)] and of 'death or CLD at 28-30 days' [summary RR 0.56 (0.40, 0.77) with a non-significant trend towards a reduction in oxygen use at 36-37 weeks postmenstrual age or discharge [summary RR 0.74 (0.55, 1.01)]. There were no differences in the rates of IVH or PVL. Of the four trials in the subgroup using surfactant routinely, three also used the HVS. The trends in results were similar with surfactant to those for the HVS subgroup analysis. One trial suggests that HFOV may reduce the cost of in-hospital care. In the subgroup of two trials (HIFI 1989, Rettwitz-Volk 1998) not using a HVS there is no effect of HFOV on the rate of CLD; however, there is an increase in the rate of PVL [summary RR 1.64 (1.02, 2.64). The overall meta-analyses is dominated by the large HIFI study which did not use the HVS recommended on the basis of animal studies, and in which surfactant was not available. Studies which used HVS have shown some benefits in short term measures of CLD without an in

The effect of postnatal steroids on growth and development.

Single courses of prenatal corticosteroids have many beneficial effects including reduction in respiratory distress syndrome, intraventricular hemorrhage and neonatal mortality. Postnatal corticosteroids, however, have both beneficial and harmful effects. The beneficial effects include shortened time on the ventilator and a reduction in chronic lung disease. Dexamethasone treatment started within the first 4 days of life is associated with an increased risk of abnormal neurodevelopment including cerebral palsy. Other adverse effects include metabolic disturbances, cardiac hypertrophy, reduced growth and gastrointestinal perforation. The risks of early dexamethasone treatment in currently used doses outweigh the benefits. Further research is needed to determine the optimal corticosteroid drug, its dose and timing of administration to maximize benefit and reduce risk to a minimum. Other non-drug interventions should be used to minimize the risk of chronic lung disease in very preterm infants.

Elective high frequency jet ventilation versus conventional ventilation for respiratory distress syndrome in preterm infants.

This section is under preparation and will be included in the next issue. The objective of this review was to determine whether the elective (commencing soon after initiation of mechanical ventilation) use of high frequency jet ventilation (HFJV), as compared to conventional ventilation (CV) in preterm infants with respiratory distress syndrome (RDS), would decrease the incidence of chronic lung disease (CLD) without adverse effects. Randomized trials from MEDLINE were identified by means of MeSH and text words 'high frequency ventilation', 'high frequency jet ventilation', 'jet ventilation' from the years 1980 to 1997. The EMBASE database, the Oxford Database of Perinatal Trials, the Neonatal Trials Register of the Neonatal Review Group of the Cochrane Collaboration and the Cochrane library were also accessed. Proceedings of recent SPR/APS meetings were hand searched. Information was obtained from experts in the field, and cross references were checked. All randomized controlled trials of elective high frequency jet ventilation versus conventional ventilation in preterm infants born at less than 35 weeks GA or with a birth weight less than 2000 gms with respiratory distress were included in the systematic review. Trials which used HFJV to 'rescue' preterm infants due to severe respiratory distress usually beyond 24 hours, and trials that used HFJV for a mandatory time period and then switched back to CV, were not included in this review. The standard methods of the Neonatal Cochrane Review Group were used, including independent trial assessment and data extraction. Data were analysed using relative risk (RR) and risk difference (RD). From 1/RD the number needed to treat (NNT) for benefits and number needed to harm (NNH) for adverse outcomes were calculated. Overall analysis of the three trials showed that HFJV is associated with a reduction in CLD at 36 weeks postmenstrual age in survivors [RR 0.58 (0.34, 0. 98), RD -0.138 (-0.268, -0.007), NNT 7 (4, 90)]. The use of home oxygen therapy was evaluated in only one study (Keszler 1997) and a lower rate was found in the HFJV group [RR 0.24 (0.07, 0.79), RD -0. 176 (-0.306, -0.047), NNT 5 (3, 21)]. Overall there was a trend towards an increase in the risk of PVL in the HFJV group, which was not significant. Subgroup analyses shows a significant increase in risk of PVL in the trial by Wiswell 1996 [RR 5.0 (1.19, 21.04), RD 0.250 (0.069, 0.431), NNH 4.0 (2.3,14.5)] where a 'low volume strategy' was the standard protocol for HFJV. In the other trial by Keszler 1997, where the intention was to use a 'high volume strategy', there was no significant difference in the incidence of PVL, RR 0.42 (0.14, 1.30). In the overall analysis, there were no significant differences in the incidence of neonatal mortality, IVH all grades or in grades 3 or 4 IVH. In the subgroup where 'low volume strategy' was used there was a non-significant trend toward an increase in risk of IVH all grades and grades 3 or 4 IVH. The overall analysis shows a benefit in pulmonary outcomes in the group electively ventilated with HFJV. Of concern is the significant increase in acute brain injury in one trial which used lower mean airway pressures when ventilating with HFJV. There are as yet no long term pulmonary or neurodevelopmental outcomes from any of the trials. Until further studies ascertain the most appropriate strategy to routinely ventilate premature infants with HFJV safely, ventilation with HFJV cannot be recommended for preterm infants with RDS.

Elective use of High Frequency Jet Ventilation (HFJV) versus Conventional Ventilation(CV) for Respiratory Distress Syndrome (RDS): Systematic review and Meta-analyses. † 1612

OBJECTIVE: To determine whether the elective (commencing soon after initiation of mechanical ventilation) use of HFJV as compared to CV in ventilated preterm infants with RDS decreases the incidence of chronic lung disease (CLD) without adverse effects. METHODS: Systematic search in accordance with Cochrane reviews. All randomized controlled trials of elective HFJV vs CV in preterm infants <35 weeks GA or <2000 gms with RDS were included. Data analyses were conducted according to the standards of Neonatal Cochrane Review Group using relative risk (RR) and number needed to treat(NNT) or harm (NNH). Preplanned subgroup analyses were trials with surfactant, high volume strategy (HVS), low volume strategy (LVS) and infants of different gestational ages and birth weight. RESULTS: Overall analyses of the three trials included in the meta-analyses1–3, showed that HFJV is associated with a reduction in CLD at 36 weeks post menstrual age (PMA) in survivors [RR 0.58 (0.34, 0.98), NNT 7 (4, 90)]. Home O2, only assessed in one trial3, is reduced [RR 0.24 (0.07,0.79), NNT 5 (3,21)]. For PVL overall RR is 1.24 (0.59, 2.61); in the subgroup where LVS was intended2 the RR is 5.0 (1.19, 21.04), NNH 4.0(2.3,14.5). In the overall analyses there were no significant differences in incidence of IVH all grades and grades 3 or 4, or in neonatal mortality. Subgroup analyses of infants at different gestational age and birthweight could not be performed. CONCLUSIONS: Overall analyses show a benefit in pulmonary outcomes (CLD at 36 wks PMA,2,3 home O2,3) in the group electively ventilated with HFJV. Of concern is the significant increase in PVL in one single centre trial which used LVS. There are as yet no long term pulmonary or neurodevelopmental outcomes from any of the trials. Until further studies ascertain the most appropriate strategy to ventilate preterm infants with HFJV safely, routine use of HFJV cannot be recommended for ventilated preterm infants with RDS.