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Background: At birth, infants' lungs are fluid-filled. For newborns to have a successful transition, this fluid must be replaced by air to enable gas exchange. Some infants are judged to have inadequate breathing at birth and are resuscitated with positive pressure ventilation (PPV). Giving prolonged (sustained) inflations at the start of PPV may help clear lung fluid and establish gas volume within the lungs., Objectives: To assess the benefits and harms of an initial sustained lung inflation (SLI) (> 1 second duration) versus standard inflations (≤ 1 second) in newborn infants receiving resuscitation with intermittent PPV., Search Methods: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 3), MEDLINE via PubMed (1966 to 1 April 2019), Embase (1980 to 1 April 2019), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 1 April 2019). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles to identify randomised controlled trials and quasi-randomised trials., Selection Criteria: Randomised controlled trials (RCTs) and quasi-RCTs comparing initial sustained lung inflation (SLI) versus standard inflations given to infants receiving resuscitation with PPV at birth., Data Collection and Analysis: We assessed the methodological quality of included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomisation, blinding, loss to follow-up, and handling of outcome data). We evaluated treatment effects using a fixed-effect model with risk ratio (RR) for categorical data; and mean standard deviation (SD), and weighted mean difference (WMD) for continuous data. We used the GRADE approach to assess the quality of evidence., Main Results: Ten trials enrolling 1467 infants met our inclusion criteria. Investigators in nine trials (1458 infants) administered sustained inflation with no chest compressions. Use of sustained inflation had no impact on the primary outcomes of this review: mortality in the delivery room (typical RR 2.66, 95% confidence interval (CI) 0.11 to 63.40 (I² not applicable); typical RD 0.00, 95% CI -0.02 to 0.02; I² = 0%; 5 studies, 479 participants); and mortality during hospitalisation (typical RR 1.09, 95% CI 0.83 to 1.43; I² = 42%; typical RD 0.01, 95% CI -0.02 to 0.04; I² = 24%; 9 studies, 1458 participants). The quality of the evidence was low for death in the delivery room because of limitations in study design and imprecision of estimates (only one death was recorded across studies). For death before discharge the quality was moderate: with longer follow-up there were more deaths (n = 143) but limitations in study design remained. Among secondary outcomes, duration of mechanical ventilation was shorter in the SLI group (mean difference (MD) -5.37 days, 95% CI -6.31 to -4.43; I² = 95%; 5 studies, 524 participants; low-quality evidence). Heterogeneity, statistical significance, and magnitude of effects of this outcome are largely influenced by a single study at high risk of bias: when this study was removed from the analysis, the size of the effect was reduced (MD -1.71 days, 95% CI -3.04 to -0.39; I² = 0%). Results revealed no differences in any of the other secondary outcomes (e.g. risk of endotracheal intubation outside the delivery room by 72 hours of age (typical RR 0.91, 95% CI 0.79 to 1.04; I² = 65%; 5 studies, 811 participants); risk of surfactant administration during hospital admission (typical RR 0.99, 95% CI 0.91 to 1.08; I² = 0%; 9 studies, 1458 participants); risk of chronic lung disease (typical RR 0.99, 95% CI 0.83 to 1.18; I² = 0%; 4 studies, 735 participants); pneumothorax (typical RR 0.89, 95% CI 0.57 to 1.40; I² = 34%; 8 studies, 1377 infants); or risk of patent ductus arteriosus requiring pharmacological treatment (typical RR 0.99, 95% CI 0.87 to 1.12; I² = 48%; 7 studies, 1127 infants). The quality of evidence for these secondary outcomes was moderate (limitations in study design ‒ GRADE) except for pneumothorax (low quality: limitations in study design and imprecision of estimates ‒ GRADE). We could not perform any meta-analysis in the comparison of the use of initial sustained inflation versus standard inflations in newborns receiving resuscitation with chest compressions because we identified only one trial for inclusion (a pilot study of nine preterm infants)., Authors' Conclusions: Our meta-analysis of nine studies shows that sustained lung inflation without chest compression was not better than intermittent ventilation for reducing mortality in the delivery room (low-quality evidence ‒ GRADE) or during hospitalisation (moderate-quality evidence ‒ GRADE), which were the primary outcomes of this review. However, the single largest study, which was well conducted and had the greatest number of enrolled infants, was stopped early for higher mortality rate in the sustained inflation group. When considering secondary outcomes, such as rate of intubation, rate or duration of respiratory support, or bronchopulmonary dysplasia, we found no benefit of sustained inflation over intermittent ventilation (moderate-quality evidence ‒ GRADE). Duration of mechanical ventilation was shortened in the SLI group (low-quality evidence ‒ GRADE); this result should be interpreted cautiously, however, as it might have been influenced by study characteristics other than the intervention. There is no evidence to support the use of sustained inflation based on evidence from our review., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Damage caused by lung overdistension (volutrauma) has been implicated in the development of bronchopulmonary dysplasia (BPD). Modern neonatal ventilation modes can target a set tidal volume as an alternative to traditional pressure-limited ventilation (PLV) using a fixed inflation pressure. Volume-targeted ventilation (VTV) aims to produce a more stable tidal volume in order to reduce lung damage and stabilise the partial pressure of carbon dioxide (pCO 2 )., Objectives: To determine whether VTV compared with PLV leads to reduced rates of death and death or BPD in newborn infants and to determine whether use of VTV affected outcomes including air leak, cranial ultrasound findings and neurodevelopment., Search Methods: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 12), MEDLINE via PubMed (1966 to 13 January 2017), Embase (1980 to 13 January 2017) and CINAHL (1982 to 13 January 2017). We also searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We contacted the principal investigators of studies to obtain supplementary information., Selection Criteria: Randomised and quasi-randomised trials comparing VTV versus PLV in infants of less than 44 weeks' postmenstrual age and reporting clinically relevant outcomes., Data Collection and Analysis: We assessed risk of bias for each trial using Cochrane methodology. We evaluated quality of evidence for each outcome using GRADE criteria. We tabulated mortality, rates of BPD, short-term clinical outcomes and long-term developmental outcomes., Statistics: for categorical outcomes, we calculated typical estimates for risk ratios (RR), risk differences (RD) and number needed to treat for an additional beneficial outcome (NNTB). For continuous variables, we calculated typical estimates for mean differences (MD). We used 95% confidence intervals (CI) and assumed a fixed-effect model for meta-analysis., Main Results: Twenty randomised trials met our inclusion criteria; 16 parallel trials (977 infants) and four cross-over trials (88 infants). No studies were blinded and the quality of evidence for outcomes assessed varied from moderate to low.We found no difference in the primary outcome, death before hospital discharge, between VTV modes versus PLV modes (typical RR 0.75, 95% CI 0.53 to 1.07; low quality evidence). However, there was moderate quality evidence that the use of VTV modes resulted in a reduction in the primary outcome, death or BPD at 36 weeks' gestation (typical RR 0.73, 95% CI 0.59 to 0.89; typical NNTB 8, 95% CI 5 to 20) and the following secondary outcomes: rates of pneumothorax (typical RR 0.52, 95% CI 0.31 to 0.87; typical NNTB 20, 95% CI 11 to 100), mean days of mechanical ventilation (MD -1.35 days, 95% CI -1.83 to -0.86), rates of hypocarbia (typical RR 0.49, 95% CI 0.33 to 0.72; typical NNTB 3, 95% CI 2 to 5), rates of grade 3 or 4 intraventricular haemorrhage (typical RR 0.53, 95% CI 0.37 to 0.77; typical NNTB 11, 95% CI 7 to 25) and the combined outcome of periventricular leukomalacia with or without grade 3 or 4 intraventricular haemorrhage (typical RR 0.47, 95% CI 0.27 to 0.80; typical NNTB 11, 95% CI 7 to 33). VTV modes were not associated with any increased adverse outcomes., Authors' Conclusions: Infants ventilated using VTV modes had reduced rates of death or BPD, pneumothoraces, hypocarbia, severe cranial ultrasound pathologies and duration of ventilation compared with infants ventilated using PLV modes. Further studies are needed to identify whether VTV modes improve neurodevelopmental outcomes and to compare and refine VTV strategies.

Background: At birth, infants' lungs are fluid-filled. For newborns to have a successful transition, this fluid must be replaced by air to enable effective breathing. Some infants are judged to have inadequate breathing at birth and are resuscitated with positive pressure ventilation (PPV). Giving prolonged (sustained) inflations at the start of PPV may help clear lung fluid and establish gas volume within the lungs., Objectives: To assess the efficacy of an initial sustained (> 1 second duration) lung inflation versus standard inflations (≤ 1 second) in newly born infants receiving resuscitation with intermittent PPV., Search Methods: We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1), MEDLINE via PubMed (1966 to 17 February 2017), Embase (1980 to 17 February 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 17 February 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles to identify randomised controlled trials and quasi-randomised trials., Selection Criteria: Randomised controlled trials (RCTs) and quasi-RCTs comparing initial sustained lung inflation (SLI) versus standard inflations given to infants receiving resuscitation with PPV at birth., Data Collection and Analysis: We assessed the methodological quality of included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomisation, blinding, loss to follow-up, and handling of outcome data). We evaluated treatment effects using a fixed-effect model with risk ratio (RR) for categorical data and mean, standard deviation (SD), and weighted mean difference (WMD) for continuous data. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach., Main Results: Eight trials enrolling 941 infants met our inclusion criteria. Investigators in seven trials (932 infants) administered sustained inflation with no chest compressions. Use of sustained inflation had no impact on the primary outcomes of this review - mortality in the delivery room (typical RR 2.66, 95% confidence interval (CI) 0.11 to 63.40; participants = 479; studies = 5; I² not applicable) and mortality during hospitalisation (typical RR 1.01, 95% CI 0.67 to 1.51; participants = 932; studies = 7; I² = 19%); the quality of the evidence was low for death in the delivery room (limitations in study design and imprecision of estimates) and was moderate for death before discharge (limitations in study design of most included trials). Amongst secondary outcomes, duration of mechanical ventilation was shorter in the SLI group (mean difference (MD) -5.37 days, 95% CI -6.31 to -4.43; participants = 524; studies = 5; I² = 95%; low-quality evidence). Heterogeneity, statistical significance, and magnitude of effects of this outcome are largely influenced by a single study: When this study was removed from the analysis, the effect was largely reduced (MD -1.71 days, 95% CI -3.04 to -0.39, I² = 0%). Results revealed no differences in any of the other secondary outcomes (e.g. rate of endotracheal intubation outside the delivery room by 72 hours of age (typical RR 0.93, 95% CI 0.79 to 1.09; participants = 811; studies = 5; I² = 0%); need for surfactant administration during hospital admission (typical RR 0.97, 95% CI 0.86 to 1.10; participants = 932; studies = 7; I² = 0%); rate of chronic lung disease (typical RR 0.95, 95% CI 0.74 to 1.22; participants = 683; studies = 5; I² = 47%); pneumothorax (typical RR 1.44, 95% CI 0.76 to 2.72; studies = 6, 851 infants; I² = 26%); or rate of patent ductus arteriosus requiring pharmacological treatment (typical RR 1.08, 95% CI 0.90 to 1.30; studies = 6, 745 infants; I² = 36%). The quality of evidence for these secondary outcomes was moderate (limitations in study design of most included trials - GRADE) except for pneumothorax (low quality: limitations in study design and imprecision of estimates - GRADE)., Authors' Conclusions: Sustained inflation was not better than intermittent ventilation for reducing mortality in the delivery room and during hospitalisation. The number of events across trials was limited, so differences cannot be excluded. When considering secondary outcomes, such as need for intubation, need for or duration of respiratory support, or bronchopulmonary dysplasia, we found no evidence of relevant benefit for sustained inflation over intermittent ventilation. The duration of mechanical ventilation was shortened in the SLI group. This result should be interpreted cautiously, as it can be influenced by study characteristics other than the intervention. Future RCTs should aim to enrol infants who are at higher risk of morbidity and mortality, should stratify participants by gestational age, and should provide more detailed monitoring of the procedure, including measurements of lung volume and presence of apnoea before or during the SLI.

Background: At birth, infants' lungs are fluid-filled; this fluid must be replaced by air to allow for effective breathing. Some infants are judged to have inadequate breathing at birth and are resuscitated with positive pressure ventilation (PPV). Giving prolonged (sustained) inflations at the start of PPV may help clear lung fluid and establish gas volume in the lungs., Objectives: To assess the efficacy of initial sustained (> one second duration) lung inflation compared to standard inflations (≤ one second) in newly born infants receiving resuscitation with intermittent PPV., Search Methods: We searched on PubMed (1966 to 1 February 2015), EMBASE (1980 to 1 February 2015) and the Cochrane Central Register of Controlled Trials (the Cochrane Library 2015). No language restrictions were applied. We searched the abstracts of the Pediatric Academic Societies (PAS) from 2000 to 2014., Selection Criteria: Randomised controlled trials (RCTs) and quasi-RCTs comparing giving initial sustained lung inflations (SLI) vs. standard inflations to infants receiving resuscitation with PPV at birth., Data Collection and Analysis: We assessed methodological quality of the included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomisation, blinding, loss to follow-up and handling of outcome data). We evaluated the treatment effect using a fixed-effect model using risk ratio for categorical data and using mean, standard deviation (SD) and weighted mean difference (WMD) for continuous data., Main Results: Two trials enrolling 352 infants met our inclusion criteria. There were no differences in the rates of mortality during hospitalisation (RR 1.59, 95% CI 0.81 to 3.10; two trials, 352 infants), intubation in the first three days of life (RR 0.85, 95% CI 0.72 to 1.02; two trials, 352 infants) or chronic lung disease (RR 1.06, 95% CI 0.79 to 1.42; two trials, 349 infants) between infants who received sustained versus standard inflations. The rate of patent ductus arteriosus (reported as need for pharmacological treatment) was higher in the sustained inflation group (RR 1.27, 95% CI 1.03 to 1.56; two trials, 352 infants)., Authors' Conclusions: At present there is insufficient evidence from clinical trials to determine the efficacy and safety of initial sustained lung inflation for newborn infants resuscitated with PPV. RCTs comparing PPV with and without sustained inflations at neonatal resuscitation are warranted.

Background: Surfactant therapy is effective in improving the outcome of very preterm infants. Trials have studied a wide variety of surfactant preparations used either to prevent or treat respiratory distress syndrome (RDS). In animal models, prophylactic surfactant leads to more homogeneous distribution and less evidence of lung damage. However, administration requires intubation and treatment of infants who will not go on to develop RDS. This is of particular concern with the advent of improved approaches to providing continuous distending pressure, particularly in the form of nasal continuous positive airway pressure (CPAP)., Objectives: To compare the effect of prophylactic surfactant administration to surfactant treatment of established RDS in very preterm infants at risk of RDS., Search Methods: We updated the search of the Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE, EMBASE, CINAHL, and clinical trials.gov register in December 13, 2011., Selection Criteria: Randomized and quasi-randomized controlled trials that compared the effects of prophylactic surfactant administration to surfactant treatment of established RDS in preterm infants at risk of RDS., Data Collection and Analysis: Data regarding clinical outcomes were extracted from the reports of the clinical trials by the reviewers. Data analysis was done in accordance with the standards of the Cochrane Neonatal Review Group., Main Results: Eleven studies were identified that met inclusion criteria [nine without routine application of continuous positive air way pressure (CPAP) in the selective treatment group; two with routine application of CPAP in the selective treatment group]The meta-analysis of studies conducted prior to the routine application of CPAP demonstrated a decrease in the risk of air leak and neonatal mortality associated with prophylactic administration of surfactant. However, the analyses of studies that allowed for routine stabilization on CPAP demonstrated a decrease in the risk of chronic lung disease or death in infants stabilized on CPAP. When all studies were evaluated together, the benefits of prophylactic surfactant could no longer be demonstrated., Authors' Conclusions: Although the early trials of prophylactic surfactant administration to infants judged to be at risk of developing RDS compared to selective use of surfactant in infants with established RDS demonstrated a decreased risk of air leak and mortality, recent large trials that reflect current practice (including greater utilization of maternal steroids and routine post delivery stabilization on CPAP) do not support these differences and demonstrate less risk of chronic lung disease or death when using early stabilization on CPAP with selective surfactant administration to infants requiring intubation.

Background: Damage caused by lung overdistension (volutrauma) has been implicated in the development bronchopulmonary dysplasia (BPD). Modern neonatal ventilation modes can target a set tidal volume as an alternative to traditional pressure-limited ventilation using a fixed inflation pressure. Volume targeting aims to produce a more stable tidal volume in order to reduce lung damage and stabilise pCO(2), Objectives: To determine whether volume-targeted ventilation (VTV) compared with pressure-limited ventilation (PLV) leads to reduced rates of death and BPD in newborn infants. Secondary objectives were to determine whether use of VTV affected outcomes including air leak, cranial ultrasound findings and neurodevelopment., Search Strategy: The search strategy comprised searches of the Cochrane Central Register of Controlled Trials, MEDLINE PubMed 1966 to January 2010, and hand searches of reference lists of relevant articles and conference proceedings., Selection Criteria: All randomised and quasi-randomised trials comparing the use of volume-targeted versus pressure-limited ventilation in infants of less than 28 days corrected age., Data Collection and Analysis: Two review authors assessed the methodological quality of eligible trials and extracted data independently. When appropriate, meta-analysis was conducted to provide a pooled estimate of effect. For categorical data the relative risk (RR) and risk difference (RD) were calculated with 95% confidence intervals. Number needed to treat was calculated when RD was statistically significant. Continuous data were analysed using weighted mean difference., Main Results: Twelve randomised trials met our inclusion criteria; nine parallel trials (629 infants) and three crossover trials (64 infants).The use of VTV modes resulted in a reduction in the combined outcome of death or bronchopulmonary dysplasia [typical RR 0.73 (95% CI 0.57 to 0.93), NNT8 (95% CI 5 to 33)]. VTV modes also resulted in reductions in pneumothorax [typical RR 0.46 (95% CI 0.25 to 0.84), NNT 17 (95% CI 10 to 100)], days of ventilation [MD -2.36 (95% CI -3.9 to -0.8)], hypocarbia [typical RR 0.56 (95%CI 0.33 to 0.96), NNT 4 (95% CI 2 to 25)] and the combined outcome of periventricular leukomalacia or grade 3-4 intraventricular haemorrhage [typical RR 0.48 (95% CI 0.28 to 0.84), NNT 11 (95% CI 7 to 50)]., Authors' Conclusions: Infants ventilated using VTV modes had reduced death and chronic lung disease compared with infants ventilated using PLV modes. Further studies are needed to identify whether VTV modes improve neurodevelopmental outcomes and to compare and refine VTV strategies.

Background: A respiratory function monitor is routinely used in neonatal intensive care units to continuously measure and display airway pressures, tidal volume and leak during ventilation. During positive pressure ventilation in the delivery room, clinical signs are used to monitor the effectiveness of ventilation. The additional use of a respiratory function monitor during positive pressure ventilation in the delivery room might help to improve the effectiveness of ventilation., Objectives: To determine whether the use of a respiratory function monitor in addition to clinical assessment compared to clinical assessment alone in newborn infants resuscitated with positive pressure ventilation reduces mortality and morbidity., Search Strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2010), MEDLINE (January 1996 to March 2010), EMBASE (January 1980 to March 2010) and CINAHL (January 1982 to March 2010). Clinical trials registers and the abstracts of the Society for Pediatric Research and the European Society for Pediatric Research were searched from 2004 to 2009. No language restrictions were applied., Selection Criteria: We planned to include randomised and quasi-randomised controlled trials and cluster trials that compared the use of a respiratory function monitor in addition to clinical assessment, compared to clinical assessment alone, in newborn infants resuscitated with positive pressure ventilation., Data Collection and Analysis: Two review authors independently evaluated the search results against the selection criteria. Data extraction and risk of bias assessment were not performed because there were no studies that met our inclusion criteria., Main Results: No studies were found meeting the criteria for inclusion in this review, Authors' Conclusions: There is insufficient evidence to determine the efficacy and safety of a respiratory function monitor in addition to clinical assessment during positive pressure ventilation at neonatal resuscitation. Randomised clinical trials comparing positive pressure ventilation with and without a respiratory function monitor in addition to clinical assessment at neonatal resuscitation are warranted.

Background: Nasal continuous positive airway pressure (NCPAP) is used to support preterm infants recently extubated, those experiencing significant apnoea of prematurity and those with respiratory distress soon after birth as an alternative to intubation and ventilation. This review focuses exclusively on identifying the most effective pressure source and interface for NCPAP delivery in preterm infants., Objectives: To determine which technique of pressure generation and which type of nasal interface for NCPAP delivery most effectively reduces the need for additional respiratory support in preterm infants extubated to NCPAP following intermittent positive pressure ventilation (IPPV) for respiratory distress syndrome (RDS) or in those treated with NCPAP soon after birth., Search Strategy: The strategy included searches of MEDLINE (1966 - 2006), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2006) CINAHL, abstracts from conference proceedings, cross-referencing of previous reviews and the use of expert informants., Selection Criteria: Randomised or quasi-randomised trials comparing different techniques of NCPAP pressure generation and/or nasal interfaces in preterm infants extubated to NCPAP following IPPV for RDS or treated with NCPAP soon after birth., Data Collection and Analysis: Data was extracted and analysed by the first three authors. Dichotomous results were analysed using the relative risk (RR), risk difference (RD) and number needed to treat (NNT)., Main Results: 1. Preterm infants being extubated to NCPAP following a period of IPPV for RDS:Meta-analysis of the results from Davis 2001 and Roukema 1999a demonstrated that short binasal prongs are more effective at preventing re-intubation than single nasal or nasopharyngeal prongs [typical RR 0.59 (CI: 0.41, 0.85), typical RD -0.21 (CI: -0.35, -0.07), NNT 5 (CI: 3, 14)]. In one study comparing short binasal prong devices (Sun 1999), the re-intubation rate was significantly lower with the Infant Flow Driver than with the Medicorp prong [RR 0.33 (CI: 0.17, 0.67), RD -0.32 (CI: -0.49, -0.15), NNT 3 (CI: 2, 7)]. The other study comparing short binasal prong devices (Infant Flow Driver versus INCA prongs, Stefanescu 2003) demonstrated no significant difference in the re-intubation rate but did show a significant reduction in the total days in hospital in the Infant Flow Driver group [MD -12.60 (95% CI: -22.81, -2.39) days].2. Preterm infants primarily treated with NCPAP soon after birth:In the one trial identified, Mazzella 2001 found a significantly lower oxygen requirement and respiratory rate in those randomised to short binasal prongs when compared with CPAP delivered via nasopharyngeal prong. The requirement for intubation beyond 48 hours from randomisation was not assessed.3. Studies randomising preterm infants to different NCPAP systems using broad inclusion criteriaThe studies of Rego 2002 and Buettiker 2004 did not examine the primary outcomes of this review. Of the secondary outcomes, Rego 2002 demonstrated a significantly higher incidence of nasal hyperaemia with the use of the Argyle prong compared with Hudson prongs [RR 2.39 (95% CI: 1.27, 4.50), RD 0.28 (95% CI: 0.10, 0.46)]. One study comparing different techniques of pressure generation is awaiting further assessment as it is currently available in abstract form only., Authors' Conclusions: Short binasal prong devices are more effective than single prongs in reducing the rate of re-intubation. Although the Infant Flow Driver appears more effective than Medicorp prongs the most effective short binasal prong device remains to be determined. The improvement in respiratory parameters with short binasal prongs suggests they are more effective than nasopharyngeal CPAP in the treatment of early RDS. Further studies incorporating longer-term outcomes are required. Studies are also needed to determine the optimal pressure source for the delivery of NCPAP.

Background: Inflammation caused by lung overdistension (volutrauma) is thought to be important in the pathogenesis of bronchopulmonary dysplasia (BPD). Preterm infants with variable lung compliance are particularly at risk. Volume-targeted neonatal ventilators have been developed as alternatives to traditional pressure-limited ventilators. They deliver consistent, appropriate tidal volumes with the aim of reducing lung damage. It is suggested that these would provide an effective, safer means of ventilating the newborn infant., Objectives: To determine whether volume-targeted ventilation compared with pressure-limited ventilation leads to reduced rates of death and BPD in newborn infants. Secondary objectives were to determine whether use of volume modes affected clinical outcomes such as incidence of airleak, growth, duration of ventilation or cranial ultrasound findings., Search Strategy: The search strategy comprised searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2004), MEDLINE PubMed 1966 to November 2004, and hand searches of reference lists of relevant articles and conference proceedings., Selection Criteria: All randomised and quasi-randomised trials comparing the use of volume-targeted versus pressure-limited ventilation in neonates in the first 28 days of life., Data Collection and Analysis: Two authors assessed the methodological quality of eligible trials and extracted data independently. When appropriate, meta-analysis was conducted to provide a pooled estimate of effect. For categorical data the relative risk (RR) and risk difference (RD) were calculated with 95% confidence intervals. Number needed to treat was calculated when RD was statistically significant. Continuous data were analysed using weighted mean difference (WMD)., Main Results: Four randomised trials were identified that addressed the outcomes of this review, recruiting a total of 178 preterm infants. All were recruited during the first 72 hours of life. Caregivers and those evaluating the outcomes of trials were not masked. All trials report high rates of follow-up, although one trial with uneven patient distribution may have had some post-randomisation attrition. No significant difference was found for death by hospital discharge, and no trials reported the combined outcome of death or BPD. When secondary outcomes were examined, pooled analysis of the trials showed that volume-targeted ventilation resulted in significant reductions in duration of ventilation [WMD -2.93 days (-4.28, -1.57)] and rates of pneumothorax [typical RR 0.23 (0.07, 0.76), RD -0.11 (-0.20, -0.03), NNT 9]. There was also a significant difference in rates of severe (Grade 3 or 4) intraventricular haemorrhage favouring the volume-targeted group [typical RR 0.32 (0.11, 0.90), RD -0.16 (-0.29, -0.03), NNT 6]. There was a reduction in the incidence of BPD (supplemental oxygen at 36 weeks) amongst surviving infants, of borderline statistical significance [typical RR 0.34 (0.11, 1.05), RD -0.14 (-0.27, 0.00), NNT=7]. No significant differences were found for failure of mode of ventilation, use of neuromuscular paralysis, patent ductus arteriosus, airleak of any sort or pulmonary interstitial emphysema alone, cranial ultrasound abnormalities or periventricular leucomalacia. None of the trials addressed growth, death after discharge from hospital or neurodevelopmental outcome., Authors' Conclusions: Although rates of death and BPD were not significantly different between the two ventilator strategies, statistically significant effects favouring volume targeting were shown for some clinically important outcomes. However, the numbers of trials and infants randomised are small and further studies are required to confirm the role of volume targeting in neonatal ventilation.

Background: Nasal continuous positive airway pressure (NCPAP) is used to support preterm infants recently extubated, those experiencing significant apnoea of prematurity and those with respiratory distress soon after birth as an alternative to intubation and ventilation. This review will focus exclusively on identifying the most effective pressure source and interface for NCPAP delivery in preterm infants., Objectives: In preterm infants extubated to NCPAP following intermittent positive pressure ventilation (IPPV) for respiratory distress syndrome (RDS) or in those treated with NCPAP soon after birth, which technique of pressure generation and which type of nasal interface for NCPAP delivery most effectively reduces the need for additional respiratory support?, Search Strategy: The strategy included searches of MEDLINE (1966-2002), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 1, 2002), CINAHL, abstracts from conference proceedings, cross-referencing of previous reviews and the use of expert informants., Selection Criteria: Randomised or quasi-randomised trials comparing different techniques of NCPAP pressure generation and/or nasal interfaces in preterm infants extubated to NCPAP following IPPV for RDS or treated with NCPAP soon after birth., Data Collection and Analysis: Data was extracted and analysed by the first three authors. Dichotomous results were analysed using the relative risk (RR), risk difference (RD) and number needed to treat (NNT)., Main Results: 1. Preterm infants being extubated to NCPAP following a period of IPPV for RDS: Meta-analysis of the results from Davis 2001 and Roukema 1999a demonstrated that short binasal prongs are more effective at preventing re-intubation than single nasal or nasopharyngeal prongs [typical RR 0.59 (CI: 0.41, 0.85), typical RD -0.21 (CI: -0.35, -0.07), NNT 5 (CI: 3, 14)]. In the single study comparing short binasal prong devices (Sun 1999) the re-intubation rate was significantly lower with the Infant Flow Driver than with the Medicorp prong [RR 0.33 (CI: 0.17, 0.67), RD -0.32 (CI: -0.49, -0.15), NNT 3 (CI: 2, 7)]. 2. Preterm infants primarily treated with NCPAP soon after birth: The one trial identified, Mazzella 2001, found a significantly lower oxygen requirement and respiratory rate in those randomised to short binasal prongs when compared with CPAP delivered via nasopharyngeal prong. The requirement for intubation beyond 48 hours from randomisation was not assessed. No studies comparing different techniques of pressure generation were identified., Reviewer's Conclusions: Short binasal prong devices are more effective than single prongs in reducing the rate of re-intubation. Although the Infant Flow Driver appears more effective than Medicorp prongs the most effective short binasal prong device remains to be determined. The improvement in respiratory parameters with short binasal prongs suggests they are more effective than nasopharyngeal CPAP in the treatment of early RDS. Further studies incorporating longer-term outcomes are required. Studies are also needed to determine the optimal pressure source for the delivery of NCPAP.

Background: Clinical trials have proven that surfactant therapy is effective in improving the immediate need for respiratory support and the clinical outcome of premature newborns (Soll 1992, Jobe 1993). Trials have studied a wide variety of surfactant preparations used either to prevent (prophylactic or delivery room administration) or treat (selective or rescue administration) respiratory distress syndrome. Using either treatment strategy, significant reductions in the incidence of pneumothorax, as well as significant improvement in survival, have been noted. It is unclear if there is an advantage to choosing either the prophylactic or selective approach to treatment, Objectives: To compare the effect of prophylactic surfactant administration to surfactant treatment of established respiratory distress syndrome in premature infants., Search Strategy: Searches were made of the Oxford Database of Perinatal Trials, Medline (MeSH terms: pulmonary surfactant; limits: age groups, newborn infants; publication type, clinical trials), previous reviews including cross-references, abstracts, conference and symposia proceedings, expert informants, and journal handsearching in the English language., Selection Criteria: Randomized controlled trials that compared the effects of prophylactic surfactant administration to surfactant treatment of established respiratory distress syndrome in premature infants were included in the analysis., Data Collection and Analysis: Data regarding clinical outcomes including the incidence of pneumothorax, pulmonary interstitial emphysema, patent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage (any grade and severe intraventricular hemorrhage), bronchopulmonary dysplasia, mortality, bronchopulmonary dysplasia or death, and retinopathy of prematurity were excerpted from the reports of the clinical trials by the reviewers. Data analysis was done in accordance with the standards of the Cochrane Neonatal Review Group., Main Results: Eight studies were identified that met inclusion criteria. The majority of included studies noted an initial improvement in the respiratory status and a decrease in the incidence of respiratory distress syndrome in infants who received prophylactic surfactant. The meta-analysis supports a decrease in the incidence of pneumothorax, a decrease in the incidence of pulmonary interstitial emphysema, a decrease in the incidence of mortality and a decrease in the incidence of bronchopulmonary dysplasia or death associated with prophylactic administration of surfactant. No significant untoward effects of prophylactic surfactant administration are noted. In a secondary analysis of infants less than 30 weeks gestation, the meta-analysis suggests a significant decrease in the risk of neonatal mortality and the risk of mortality or bronchopulmonary dysplasia., Reviewer's Conclusions: Prophylactic surfactant administration to infants judged to be at risk of developing respiratory distress syndrome (infants less than 30-32 weeks gestation), compared to selective use of surfactant in infants with established RDS, has been demonstrated to improve clinical outcome. Infants who receive prophylactic surfactant have a decreased risk of pneumothorax, a decreased risk of pulmonary interstitial emphysema and a decreased risk of mortality. However, it remains unclear exactly which criteria should be used to judge "at risk" infants who would require prophylactic surfactant administration.

Background: This section is under preparation and will be included in the next issue., Objectives: To compare the effect of prophylactic surfactant administration to surfactant treatment of established respiratory distress syndrome in premature infants., Search Strategy: Searches were made of the Oxford Database of Perinatal Trials, Medline (MeSH terms: pulmonary surfactant; limits: age groups, newborn infants), previous reviews including cross-references, abstracts, conference and symposia proceedings, expert informants, and journal handsearching in the English language., Selection Criteria: Randomized controlled trials which compared the effects of prophylactic surfactant administration to surfactant treatment of established respiratory distress syndrome in premature infants were included in the analysis., Data Collection and Analysis: Data regarding clinical outcomes including the incidence of pneumothorax, pulmonary interstitial emphysema, patent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage (any grade and severe intraventricular hemorrhage), bronchopulmonary dysplasia, mortality, bronchopulmonary dysplasia or death, and retinopathy of prematurity were excerpted from the reports of the clinical trials by the reviewers. Data analysis was done in accordance with the standards of the Cochrane Neonatal Review Group., Main Results: The majority of included studies noted an initial improvement in the respiratory status and a decrease in the incidence of respiratory distress syndrome in infants who received prophylactic surfactant. The meta-analysis supports a decrease in the incidence of pneumothorax, a decrease in the incidence of pulmonary interstitial emphysema, a decrease in the incidence of mortality and a decrease in the incidence of bronchopulmonary dysplasia or death associated with prophylactic administration of surfactant. No significant untoward effects of prophylactic surfactant administration are noted., Reviewer's Conclusions: Prophylactic surfactant administration to infants judged to be at risk of developing respiratory distress syndrome (intubated infants less than 30-32 weeks gestation) has been demonstrated to improve clinical outcome. Infants who receive prophylactic surfactant have a decreased incidence of pneumothorax, a decreased incidence of pulmonary interstitial emphysema and a decreased incidence of mortality. However, it remains unclear exactly which criteria should be used to judge "at risk" infants who would require prophylactic surfactant administration.

Eighteen children with acute myeloid leukemia have been treated with a four-drug protocol using cytosine arabinoside, daunorubicin, prednisolone, and mercaptopurine or thioguanine. The initial remission rate overall was 78%. Of 15 children who completed a week's treatment, i.e. one complete cycle, 14 entered complete remission (93%). The median survival was 7 months, and the median survival for those entering remission was 12 1/2 months.