Publications by authors named "Risha Bhatia"

25 Publications

  • Page 1 of 1

Introduction of a Quality Improvement Bundle Is Associated with Reduced Exposure to Mechanical Ventilation in Very Preterm Infants.

Neonatology 2021 Sep 1:1-8. Epub 2021 Sep 1.

Department of Paediatrics, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Victoria, Australia.

Introduction: Exposure to mechanical ventilation (MV) is a risk factor for bronchopulmonary dysplasia (BPD) in very preterm infants (VPTIs). We assessed the impact of a quality improvement (QI) bundle in VPTIs (<32 week gestation) on exposure to MV.

Methods: We introduced a QI bundle consisting of deferred cord clamping (DCC), nasal bubble continuous positive airway pressure (bCPAP) in the delivery room (DR), and minimally invasive surfactant therapy (MIST). We compared respiratory outcomes and neonatal morbidity in historical pre-QI (July-December 2017) and prospective post-QI (February-July 2019) cohorts (QICs) of VPTIs. We pre-specified an adjusted analysis to account for the effects of gestational age, sex, antenatal steroids, and any demographic data that significantly differed between cohorts.

Results: The pre-QI and post-QICs included 87 and 98 VPTIs, respectively. The post-QIC had decreased rates of MV in the DR (adjusted odds ratio [aOR] 0.26, 95% confidence interval [CI] 0.09-0.71), in the first 72 h of life (aOR 0.27, 95% CI 0.11-0.62) and during admission (aOR 0.28, 95% CI 0.12-0.66). Rates of BPD, combined BPD/death, and BPD severity were similar. The post-QIC was less likely to be discharged with home oxygen (aOR 0.27, 95% CI 0.08-0.91). Necrotising enterocolitis grade ≥2 increased (aOR 19.01, 95% CI 1.93-188.6) in the post-QIC.

Conclusion: In this rapid-cycle QI study, implementation of a QI bundle consisting of DCC, early nasal bCPAP, and MIST in VPTIs was associated with reduced rates of MV in the DR, in the first 72 h of life and during admission, and reduced need for home oxygen.
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http://dx.doi.org/10.1159/000518392DOI Listing
September 2021

Extubation generates lung volume inhomogeneity in preterm infants.

Arch Dis Child Fetal Neonatal Ed 2021 Jun 23. Epub 2021 Jun 23.

Newborn Research, The Royal Women's Hospital, Parkville, Victoria, Australia.

Objective: To evaluate the feasibility of electrical impedance tomography (EIT) to describe the regional tidal ventilation (V) and change in end-expiratory lung volume (EELV) patterns in preterm infants during the process of extubation from invasive to non-invasive respiratory support.

Design: Prospective observational study.

Setting: Single-centre tertiary neonatal intensive care unit.

Patients: Preterm infants born <32 weeks' gestation who were being extubated to nasal continuous positive airway pressure as per clinician discretion.

Interventions: EIT measurements were taken in supine infants during elective extubation from synchronised positive pressure ventilation (SIPPV) before extubation, during and then at 2 and 20 min after commencing nasal continuous positive applied pressure (nCPAP). Extubation and pressure settings were determined by clinicians.

Main Outcome Measures: Global and regional ΔEELV and ΔV, heart rate, respiratory rate and oxygen saturation were measured throughout.

Results: Thirty infants of median (range) 2 (1, 21) days were extubated to a median (range) CPAP 7 (6, 8) cm HO. SpO/FiO ratio was a mean (95% CI) 50 (35, 65) lower 20 min after nCPAP compared with SIPPV. EELV was lower at all points after extubation compared with SIPPV, and EELV loss was primarily in the ventral lung (p=0.04). V was increased immediately after extubation, especially in the central and ventral regions of the lung, but the application of nCPAP returned V to pre-extubation patterns.

Conclusions: EIT was able to describe the complex lung conditions occurring during extubation to nCPAP, specifically lung volume loss and greater use of the dorsal lung. EIT may have a role in guiding peri-extubation respiratory support.
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http://dx.doi.org/10.1136/archdischild-2021-321788DOI Listing
June 2021

Protocol for a randomised controlled trial comparing two CPAP levels to prevent extubation failure in extremely preterm infants.

BMJ Open 2021 06 23;11(6):e045897. Epub 2021 Jun 23.

Monash Newborn, Monash Newborn at Monash Children's Hospital, Clayton, Victoria, Australia.

Introduction: Respiratory distress syndrome is a complication of prematurity and extremely preterm infants born before 28 weeks' gestation often require endotracheal intubation and mechanical ventilation. In this high-risk population, mechanical ventilation is associated with lung injury and contributes to bronchopulmonary dysplasia. Therefore, clinicians attempt to extubate infants as quickly and use non-invasive respiratory support such as nasal continuous positive airway pressure (CPAP) to facilitate the transition. However, approximately 60% of extremely preterm infants experience 'extubation failure' and require reintubation. While CPAP pressures of 5-8 cm H2O are commonly used, the optimal CPAP pressure is unknown, and higher pressures may be beneficial in avoiding extubation failure. Our trial is the Extubation CPAP Level Assessment Trial (ÉCLAT). The aim of this trial is to compare higher CPAP pressures 9-11 cm H2O with a current standard pressures of 6-8 cmH2O on extubation failure in extremely preterm infants.

Methods And Analysis: 200 extremely preterm infants will be recruited prior to their first extubation from mechanical ventilation to CPAP. This is a parallel group randomised controlled trial. Infants will be randomised to one of two set CPAP pressures: CPAP 10 cmH2O (intervention) or CPAP 7 cmH2O (control). The primary outcome will be extubation failure (reintubation) within 7 days. Statistical analysis will follow standard methods for randomised trials on an intention to treat basis. For the primary outcome, this will be by intention to treat, adjusted for the prerandomisation strata (GA and centre). We will use the appropriate parametric and non-parametric statistical tests.

Ethics And Dissemination: Ethics approval has been granted by the Monash Health Human Research Ethics Committees. Amendments to the trial protocol will be submitted for approval. The findings of this study will be written into a clinical trial report manuscript and disseminated via peer-reviewed journals (on-line or in press) and presented at national and international conferences.ACTRN12618001638224; pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-045897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230987PMC
June 2021

Staff awareness and bundling reduce skin breaks and blood tests in neonatal intensive care.

J Paediatr Child Health 2021 Sep 2;57(9):1485-1489. Epub 2021 May 2.

Monash Newborn, Monash Children's Hospital, Melbourne, Victoria, Australia.

Aim: Skin breaks (SBs) for procedures and blood sampling are common in neonatal intensive care units (NICU), contributing to pain, infection risk and anaemia. We aimed to document their prevalence, identify areas for improvement and, through staff awareness, reduce their frequency.

Methods: Quality improvement project via prospective audit at a tertiary-level NICU in Australia was conducted. All infants admitted to the NICU for >24 h during two audit periods were included in the study. A specifically designed bedside audit tool was used to prospectively document all SB and blood tests performed on infants during a 4-week audit period (audit 1). Results were reviewed to identify areas for improvement, and disseminated to staff at unit meetings, shift handover and email. Following education and awareness, the audit was repeated (audit 2), and data were compared. Frequency of SB and blood tests performed was measured. Data were tested for normality and analysed using parametric or non-parametric tests where appropriate.

Results: There were 52 NICU admissions during each audit period (104 total), with 34 (65%) and 31 (60%) having audit sheets completed, respectively. Median (interquartile range) gestational age and mean (standard deviation) birthweight were 29 (26.3-35) weeks and 1836 (1185) g for audit 1, 30 (28.5-31.5) weeks and 1523 (913) g for audit 2. The reduction in total blood tests (mean) was 36.3%, skin breaks per admitted baby day reduced by 60% and total blood volume sampled (mean) by 37.7%.

Conclusions: A quality improvement project by prospective audit and staff education was associated with reductions in frequency of skin breaks and blood tests in the NICU.
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http://dx.doi.org/10.1111/jpc.15532DOI Listing
September 2021

Nucleated Red Blood Cells as Markers of Perinatal Adaptation in Preterm Neonates Receiving Minimally Invasive Surfactant Therapy.

Am J Perinatol 2021 Mar 23. Epub 2021 Mar 23.

Monash Newborn, Monash Children's Hospital, Melbourne, Australia.

Objective:  The study aimed to assess the association of nucleated red blood cells (NRBC), a surrogate of intrauterine hypoxia, and elevated pulmonic vascular resistance (E-PVR) and oxygen requirement after minimally invasive surfactant therapy (MIST).

Study Design:  Retrospective study of a cohort of preterm neonates that received MIST in a single unit.

Results:  NRBC were measured in 65 of 75 (87%) neonates administered MIST during the period. In total, 22 of 65 (34%) infants had pre-MIST echocardiography (ECHO).Neonates with elevated NRBC (predefined as >5 × 10/L,  = 16) required higher post-MIST fraction of inspired oxygen (FiO) than neonates with normal NRBC (<1 × 10/L,  = 17; FiO= 0.31 ± 0.10 and 0.24 ± 0.04, respectively,  = 0.02).NRBC correlated positively with % of time in right to left ductal shunt (r = 0.51,  = 0.052) and inversely with right ventricular stroke volume (r = -0.55,  = 0.031) and time to peak velocity to right ventricular ejection time ratio (r = -0.62,  < 0.001).

Conclusion:  Elevated NRBC are associated with elevated FiO after MIST and elevated E-PVR. Intrauterine hypoxia may impact postnatal circulatory adaptations and oxygen requirement.

Key Points: · Post-MIST FiO2 requirements are significantly higher in infants with elevated NRBC.. · NRBC correlates positively with elevated PVR in neonates requiring.. · Intrauterine hypoxia may play a role in postnatal circulatory adaptations in neonates with RDS..
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http://dx.doi.org/10.1055/s-0041-1726317DOI Listing
March 2021

Predictors and outcomes of extubation failure in extremely preterm infants.

J Paediatr Child Health 2021 06 23;57(6):913-919. Epub 2021 Jan 23.

Monash Newborn, Monash Children's Hospital, Melbourne, Victoria, Australia.

Aim: To determine predictors and outcomes of extubation failure in extremely preterm (EP) infants born <28 weeks' gestational age (GA).

Methods: Retrospective clinical audit across two tertiary-level neonatal intensive care units in Melbourne, Australia. Two-hundred and four EP infants who survived to their first extubation from mechanical ventilation. Extubation failure (re-intubation) within 7 days after the first extubation.

Results: Lower GA (odds ratio [OR] 0.71, 95% confidence interval (CI), 0.61-0.89, P < 0.001) and higher pre-extubation measured mean airway pressure (MAP) on the mechanical ventilator (OR 1.9 [95% CI 1.41-2.51], P < 0.001) predicted extubation failure. The area under a receiver operating characteristic curve for GA and MAP was 0.77 (95% CI 0.70-0.82). After adjustment for GA, infants who experienced extubation failure had higher rates of bronchopulmonary dysplasia (P < 0.001), post-natal systemic corticosteroid treatment (P < 0.001), airway trauma (P < 0.003), longer durations of treatment with mechanical ventilation (P < 0.001), non-invasive respiratory support (P < 0.001), supplemental oxygen therapy (P = 0.05) and longer hospitalisation (P = 0.025).

Conclusions: Lower GA and higher pre-extubation measured MAP were predictive of extubation failure within 7 days in extremely preterm infants. Extubation failure was associated with increased morbidity and extended periods of respiratory support and hospitalisation.
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http://dx.doi.org/10.1111/jpc.15356DOI Listing
June 2021

Outcomes after Introduction of Minimally Invasive Surfactant Therapy in Two Australian Tertiary Neonatal Units.

J Pediatr 2021 02 14;229:141-146. Epub 2020 Oct 14.

Newborn Research Centre and Neonatal Services, The Royal Women's Hospital, Parkville, Victoria, Australia; Department of Obstetrics and Gynecology, The University of Melbourne, Parkville, Victoria, Australia; Clinical Sciences, Murdoch Children's Research Institute, Parkville, Victoria, Australia.

Objective: To assess the procedural and clinical outcomes associated with the introduction of minimally invasive surfactant therapy (MIST) into standard care at 2 tertiary Australian neonatal intensive care units.

Study Design: A prospective audit was designed before the introduction of MIST in 2018, with data collected over a period of 18 months. Procedural data were completed by the clinical team performing MIST, including clinical observations, medication use, and adverse events. The audit team collected demographic data and subsequent clinical outcomes from medical records.

Results: There were 135 MIST procedures recorded in 122 infants. For the included infants, the median gestation was 30 weeks (IQR, 27 to 32 weeks) and birth weight was 1439 g (IQR, 982-1958 g). During the MIST procedure, desaturation to a peripheral oxygen saturation of <80% was common, occurring in 75.2% of procedures. Other adverse events included need for positive pressure ventilation (10.6%) and bradycardia <100 beats per minute (13.3%). The use of atropine premedication was associated with a significantly lower incidence of bradycardia: 8.6% vs 52.9% (P < .01). Senior clinicians demonstrated higher rates of procedural success. The majority of infants (63.9%) treated with MIST did not require subsequent intubation and mechanical ventilation.

Conclusions: MIST can be successfully introduced in neonatal units with limited experience of this technique. The use of atropine premedication decreases the incidence of bradycardia during the procedure. Success rates can be optimized by limiting MIST to clinicians with greater competence in endotracheal intubation.
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http://dx.doi.org/10.1016/j.jpeds.2020.10.025DOI Listing
February 2021

Cardiovascular response and sequelae after minimally invasive surfactant therapy in growth-restricted preterm infants.

J Perinatol 2020 08 6;40(8):1178-1184. Epub 2020 May 6.

Monash Newborn, Monash Children's Hospital, Melbourne, Vic, Australia.

Objective: To study cardiovascular response to minimally invasive surfactant therapy in preterm infants with and without foetal growth restriction (FGR).

Design: Poractant alfa was administered and echocardiograms were performed before and 30 min after. FGR infants were compared with those appropriate for gestational age (AGA).

Results: Ten FGR infants were compared with 20 AGA infants (gestation [weeks], 28.9 ± 2 vs. 28.6 ± 1, p = 0.55 and birthweight [g], 813 ± 157 vs. 1141 ± 257, p = 0.01, respectively). The change in echocardiographic parameters was more prominent in AGA infants ([global contractility] fractional area change [FAC, %], FGR, 24.7 ± 2.2 to 27.9 ± 0.4, p = 0.08 vs. AGA, 26.6 ± 3 to 30.5 ± 1, p < 0.01, and [longitudinal contractility] tricuspid annular plane systolic excursion [mm], FGR, 3.9 ± 0.3 to 4.6 ± 0.5, p = 0.003 vs. AGA, 4.6 ± 0.3 to 5.5 ± 0.4, p = 0.0001). Significant difference was noted for change in FAC (%), FGR 2.1 ± 1.7 vs. AGA 4.1 ± 1.2, p = 0.02.

Conclusions: Differential cardiovascular response to minimally invasive surfactant therapy amongst FGR infants may reflect an in-utero maladaptive state.
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http://dx.doi.org/10.1038/s41372-020-0682-5DOI Listing
August 2020

Tools to assess lung aeration in neonates with respiratory distress syndrome.

Acta Paediatr 2020 04 3;109(4):667-678. Epub 2019 Oct 3.

Department of Paediatrics, Monash University, Melbourne, Vic., Australia.

Aim: Respiratory distress syndrome is a common condition among preterm neonates, and assessing lung aeration assists in diagnosing the disease and helping to guide and monitor treatment. We aimed to identify and analyse the tools available to assess lung aeration in neonates with respiratory distress syndrome.

Methods: A systematic review and narrative synthesis of studies published between January 1, 2004, and August 26, 2019, were performed using the OVID Medline, PubMed, Embase and Scopus databases.

Results: A total of 53 relevant papers were retrieved for the narrative synthesis. The main tools used to assess lung aeration were respiratory function monitoring, capnography, chest X-rays, lung ultrasound, electrical impedance tomography and respiratory inductive plethysmography. This paper discusses the evidence to support the use of these tools, including their advantages and disadvantages, and explores the future of lung aeration assessments within neonatal intensive care units.

Conclusion: There are currently several promising tools available to assess lung aeration in neonates with respiratory distress syndrome, but they all have their limitations. These tools need to be refined to facilitate convenient and accurate assessments of lung aeration in neonates with respiratory distress syndrome.
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http://dx.doi.org/10.1111/apa.15028DOI Listing
April 2020

Cardiorespiratory Physiology following Minimally Invasive Surfactant Therapy in Preterm Infants.

Neonatology 2019 5;116(3):278-285. Epub 2019 Sep 5.

Monash Newborn, Monash Children's Hospital, Melbourne, Victoria, Australia.

Introduction: Surfactant replacement therapy through the endotracheal tube has been shown to improve lung compliance and reduce pulmonary pressures. Minimally invasive surfactant therapy (MIST) combines the benefits of continuous positive airway pressure (CPAP) and surfactant for spontaneously breathing preterm infants. We aimed to characterize the haemodynamic changes accompanying the first dose of MIST in preterm infants.

Methods: Poractant alfa (200 mg/kg) was administered as MIST while on CPAP support. Echocardiograms were performed before (T1) and 30 (T2) and 60 min (T3) after MIST to assess serial change.

Results: Twenty infants (mean gestational age 29.5 ± 2.8 weeks, median birth weight 1,102 g, IQR 840-1,940) received MIST at a median age of 16 h (IQR 3-24). FiO2 decreased significantly at 30 min (0.41 ± 0.08 to 0.27 ± 0.03, p < 0.001). Significant changes were noted at T2 for ductal parameters (decreased % time right to left shunt: 25% [15-33] to 14.5% [6-22], p = 0.013). Reduced pulmonary vascular resistance (PVR; increased pulmonary artery time velocity ratio 0.23 ± 0.05 to 0.28 ± 0.04 ms, p = 0.004) and improved longitudinal (tricuspid annular plane systolic excursion 4.5 ± 0.8 to 5.3 ± 0.9 mm, p = 0.004) and global (fractional area change 25 ± 2.3 vs. 27 ± 2%, p = 0.002) ventricular function were noted.

Conclusions: This is the first study assessing cardiovascular adaptation to MIST, a procedure fast gaining acceptance in the neonatal community. Increased pulmonary blood flow is likely due to a combined effect of increased ductal flow, reduced PVR, and increased ventricular function.
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http://dx.doi.org/10.1159/000502040DOI Listing
June 2020

Surfactant phospholipid composition of gastric aspirate samples differs between male and female very preterm infants.

Pediatr Res 2017 Nov 2;82(5):839-849. Epub 2017 Aug 2.

Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.

BackgroundAmong preterm infants, males have a greater incidence of respiratory distress and death than do females born at the same gestational age, likely due to sex-related differences in lung maturation. Our aim was to determine whether surfactant phospholipid composition differs between male and female preterm infants.MethodsGastric aspirate samples from male and female infants born between 25 and 30 weeks of gestation at The Royal Women's Hospital, Melbourne, Australia, were collected within 1 h after birth. Phospholipid composition was analyzed by electrospray ionization tandem mass spectrometry.ResultsPreterm males had higher proportions of total phosphatidylinositol (PI) and phosphatidylserine 36:2, lower proportions of total sphingomyelin (S) and S 33:1 and 35:1, and a greater phosphatidylcholine (PC)/S ratio than did females. The proportions of PC 30:0, PC 34:0, PC 34:2, PC 36:2, PC 36:3, and PC 38:2 differed between the sexes at different gestational weeks of birth; the proportion of PC 32:0 (dipalmitoylphosphatidylcholine) in males was lower than that in females at 25 weeks of gestation but higher at 27 weeks.ConclusionPhospholipid composition in pulmonary surfactant is different between male and female preterm infants of the same gestational age, which may contribute to the increased risk for respiratory morbidities in one sex.
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http://dx.doi.org/10.1038/pr.2017.147DOI Listing
November 2017

Regional Volume Characteristics of the Preterm Infant Receiving First Intention Continuous Positive Airway Pressure.

J Pediatr 2017 08 22;187:80-88.e2. Epub 2017 May 22.

Newborn Research, The Royal Women's Hospital, Melbourne, Australia; Neonatal Research, Murdoch Childrens Research Institute, Melbourne, Australia; The University of Melbourne, Melbourne, Australia; Department of Neonatology, The Royal Children's Hospital, Melbourne, Australia.

Objective: To determine whether applying nasal continuous positive airway pressure (CPAP) using systematic changes in continuous distending pressure (CDP) results in a quasi-static pressure-volume relationship in very preterm infants receiving first intention CPAP in the first 12-18 hours of life.

Study Design: Twenty infants at <32 weeks' gestation with mild respiratory distress syndrome (RDS) managed exclusively with nasal CPAP had CDP increased from 5 to 8 to 10 cmHO, and then decreased to 8 cmHO and returned to baseline CDP. Each CDP was maintained for 20 min. At each CDP, relative impedance change in end-expiratory thoracic volume (ΔZEEV) and tidal volume (ΔZV) were measured using electrical impedance tomography. Esophageal pressure (P) was measured as a proxy for intrapleural pressure to determine transpulmonary pressure (P).

Results: Overall, there was a relationship between P and global ΔZEEV representing the pressure-volume relationship in the lungs. There were regional variations in ΔZEEV, with 13 infants exhibiting hysteresis with the greatest gains in EEV and tidal volume in the dependent lung with no hemodynamic compromise. Seven infants did not demonstrate hysteresis during decremental CDP changes.

Conclusion: It was possible to define a pressure-volume relationship of the lung and demonstrate reversal of atelectasis by systematically manipulating CDP in most very preterm infants with mild RDS. This suggests that CDP manipulation can be used to optimize the volume state of the preterm lung.
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http://dx.doi.org/10.1016/j.jpeds.2017.04.046DOI Listing
August 2017

Personal smartphones for neonatal diagnostic imaging: A prospective crossover study.

J Paediatr Child Health 2017 Apr 14;53(4):343-347. Epub 2017 Feb 14.

Department of Newborn Research, The Royal Women's Hospital, Melbourne, Victoria, Australia.

Aim: Neonatal clinicians may be asked to review X-ray images when unable to directly access the original image. Transmitting an X-ray image to a smartphone is a technique increasingly being used by clinicians in a number of settings. Minimal data exist on its use in the neonatal setting. Our aim was to compare the ability of neonatal clinicians to correctly diagnose a pneumothorax from a chest radiograph (CXR) viewed on a smartphone, paralleled with the same image viewed on a computer screen.

Methods: We investigated the accuracy, sensitivity, specificity, positive predictive value and negative predicative value of two methods of viewing CXR images to diagnose pneumothorax, compared with a gold standard radiologist report. Clinicians were presented with 40 CXR images on two occasions, at least 1 week apart. Images were viewed once on a smartphone and once on a computer screen. Both the viewing method and viewing order of the images were randomised. The clinical details of the infant at the time the CXR was taken were provided, and participants were asked if a pneumothorax was present.

Results: Twenty-one clinicians viewed all CXR images using both viewing methods (840 paired observations). There was no difference in accuracy of detecting pneumothorax between viewing methods, 81% correctly identified a pneumothorax using the smartphone, versus 80% using the computer screen (P = 0.40 (95% CI), difference -4 to 1.5%).

Conclusion: Diagnosis of neonatal pneumothorax was as accurate using a smartphone as viewing CXR images displayed on a computer screen when clinicians were presented with X-rays with diagnosis of pneumothorax.
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http://dx.doi.org/10.1111/jpc.13467DOI Listing
April 2017

Phototherapy in transport for neonates with unconjugated hyperbilirubinaemia.

J Paediatr Child Health 2016 Jan 19;52(1):67-71. Epub 2015 Aug 19.

Paediatric Infant Perinatal Emergency Retrieval Service, Royal Children's Hospital, Melbourne, Victoria, Australia.

Aim: In Victoria, neonates with severe unconjugated hyperbilirubinaemia at risk of requiring exchange transfusion are retrieved by the Paediatric Infant Perinatal Emergency Retrieval Service and transferred to a Neonatal Intensive Care Unit where an exchange transfusion can be performed if necessary. Transfer may result in prolonged periods without phototherapy in neonates at risk of developing bilirubin encephalopathy. We aimed to describe our experience of the introduction of phototherapy using a portable phototherapy unit during transport.

Methods: Neonates with a primary diagnosis of severe unconjugated hyperbilirubinaemia were identified from the Paediatric Infant Perinatal Emergency Retrieval clinical database over an 11-year period. Demographic and clinical data including gestation, age at transport, serum bilirubin levels pre- and post-transport, use of phototherapy during transport (PTDT), likely diagnosis, and use of exchange transfusion were included.

Results: A total of 147 neonates were included with 104 neonates receiving PTDT and 43 who did not. Neonates who received PTDT were less likely to require exchange transfusion, 19.2% versus 34.9%, odds ratio 0.44 (95% CI 0.2-0.98), P = 0.05. However, after correction for factors appearing to be related to use of exchange transfusion, the odds ratio increased to 0.58 (95% CI 0.21-1.63), P = 0.3. There was a greater reduction in the pre- to post-transport total serum bilirubin levels (μmol/L) for the group receiving PTDT (mean 46.3, SD 64.6) versus no PTDT (mean 26.1, SD 62.5), but this did not reach significance, P = 0.08.

Conclusions: Phototherapy during neonatal transport is feasible and safe and may result in a decreased requirement for subsequent exchange transfusion.
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http://dx.doi.org/10.1111/jpc.12984DOI Listing
January 2016

Pressure-limited sustained inflation vs. gradual tidal inflations for resuscitation in preterm lambs.

J Appl Physiol (1985) 2015 Apr 29;118(7):890-7. Epub 2015 Jan 29.

Centre for Neonatal Research and Education, School of Paediatrics and Child Health, University of Western Australia, Perth, Australia; School of Anatomy, Physiology and Human Biology, The University of Western Australia, Crawley, Western Australia, Australia;

Support of the mechanically complex preterm lung needs to facilitate aeration while avoiding ventilation heterogeneities: whether to achieve this gradually or quickly remains unclear. We compared the effect of gradual vs. constant tidal inflations and a pressure-limited sustained inflation (SI) at birth on gas exchange, lung mechanics, gravity-dependent lung volume distribution, and lung injury in 131-day gestation preterm lambs. Lambs were resuscitated with either 1) a 20-s, 40-cmH2O pressure-limited SI (PressSI), 2) a gradual increase in tidal volume (Vt) over 5-min from 3 ml/kg to 7 ml/kg (IncrVt), or 3) 7 ml/kg Vt from birth. All lambs were subsequently ventilated for 15 min with 7 ml/kg Vt with the same end-expiratory pressure. Lung mechanics, gas exchange and spatial distribution of end-expiratory volume (EEV), and tidal ventilation (electrical impedance tomography) were recorded regularly. At 15 min, early mRNA tissue markers of lung injury were assessed. The IncrVt group resulted in greater tissue hysteresivity at 5 min (P = 0.017; two-way ANOVA), higher alveolar-arterial oxygen difference from 10 min (P < 0.01), and least uniform gravity-dependent distribution of EEV. There were no other differences in lung mechanics between groups, and the PressSI and 7 ml/kg Vt groups behaved similarly throughout. EEV was more uniformly distributed, but Vt least so, in the PressSI group. There were no differences in mRNA markers of lung injury. A gradual increase in Vt from birth resulted in less recruitment of the gravity-dependent lung with worse oxygenation. There was no benefit of a SI at birth over mechanical ventilation with 7 ml/kg Vt.
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http://dx.doi.org/10.1152/japplphysiol.00985.2014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4459928PMC
April 2015

Neonatal resuscitation in resource-limited settings: titrating oxygen delivery without an oxygen blender.

J Pediatr 2014 Aug 24;165(2):256-260.e1. Epub 2014 May 24.

Neonatal Services, The Royal Women's Hospital, Melbourne, Australia; The University of Melbourne, Victoria, Australia; Murdoch Children's Research Institute, Melbourne, Australia.

Objective: To test whether 4 commonly used self-inflating bags with a reservoir in situ can reliably deliver different oxygen concentrations (21%-100%) using a portable oxygen cylinder with flows of ≤5 L/min.

Study Design: Four self-inflating bags (from Laerdal, Ambu, Parker Healthcare, and Mayo Healthcare) were tested to provide positive pressure ventilation to a manikin at 60 inflations/min by 4 operators. Oxygen delivery was measured for 2 minutes, combining oxygen flows (0.25, 0.5, 1, 5 L/min) and peak inspiratory pressures (PIPs 20-25, 35-40 cmH2O).

Results: Combinations (n=128) were performed twice. Oxygen delivery depended upon device, oxygen flow, and PIP. All self-inflating bags delivered mean oxygen concentrations of <40% with 0.25 L/min, regardless of PIP. Three self-inflating bags delivered ≤40% with flow 0.5 L/min at PIP 35-40 cmH2O, whereas all delivered >40% at PIP 20-25 cmH2O. With 1 L/min, 3 self-inflating bags delivered 40%-60% at PIP 35-40 cmH2O and all delivered >60% at PIP 20-25 cmH2O. With 5 L/min, all self-inflating bags delivered close to or 100%, regardless of PIP. Differences in oxygen delivery between self-inflating bags were statistically significant (P<.001) even when differences were not clinically important.

Conclusion: Self-inflating bags with a reservoir in situ can deliver a variety of oxygen concentrations without a blender, from <40% with 0.25 L/min oxygen flow to 100% with 5 L/min. The adjustment of oxygen flow may be a useful method of titrating oxygen in settings where air-oxygen blenders are unavailable.
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http://dx.doi.org/10.1016/j.jpeds.2014.04.020DOI Listing
August 2014

Pressure- versus volume-limited sustained inflations at resuscitation of premature newborn lambs.

BMC Pediatr 2014 Feb 15;14:43. Epub 2014 Feb 15.

Centre for Neonatal Research and Education, School of Paediatrics and Child Health, University of Western Australia, Perth, Australia.

Background: Sustained inflations (SI) are advocated for the rapid establishment of FRC after birth in preterm and term infants requiring resuscitation. However, the most appropriate way to deliver a SI is poorly understood. We investigated whether a volume-limited SI improved the establishment of FRC and ventilation homogeneity and reduced lung inflammation/injury compared to a pressure-limited SI.

Methods: 131 d gestation lambs were resuscitated with either: i) pressure-limited SI (PressSI: 0-40 cmH2O over 5 s, maintained until 20 s); or ii) volume-limited SI (VolSI: 0-15 mL/kg over 5 s, maintained until 20 s). Following the SI, all lambs were ventilated using volume-controlled ventilation (7 mL/kg tidal volume) for 15 min. Lung mechanics, regional ventilation distribution (electrical impedance tomography), cerebral tissue oxygenation index (near infrared spectroscopy), arterial pressures and blood gas values were recorded regularly. Pressure-volume curves were performed in-situ post-mortem and early markers of lung injury were assessed.

Results: Compared to a pressure-limited SI, a volume-limited SI had increased pressure variability but reduced volume variability. Each SI strategy achieved similar end-inflation lung volumes and regional ventilation homogeneity. Volume-limited SI increased heart-rate and arterial pressure faster than pressure-limited SI lambs, but no differences were observed after 30 s. Volume-limited SI had increased arterial-alveolar oxygen difference due to higher FiO2 at 15 min (p = 0.01 and p = 0.02 respectively). No other inter-group differences in arterial or cerebral oxygenation, blood pressures or early markers of lung injury were evident.

Conclusion: With the exception of inferior oxygenation, a sustained inflation targeting delivery to preterm lambs of 15 mL/kg volume by 5 s did not influence physiological variables or early markers of lung inflammation and injury at 15 min compared to a standard pressure-limited sustained inflation.
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http://dx.doi.org/10.1186/1471-2431-14-43DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3937019PMC
February 2014

Optimal mean airway pressure during high-frequency oscillatory ventilation determined by measurement of respiratory system reactance.

Pediatr Res 2014 Apr 27;75(4):493-9. Epub 2013 Dec 27.

1] Neonatal Research, Murdoch Childrens Research Institute, Melbourne, Victoria, Australia [2] Department of Neonatology, Royal Children's Hospital, Melbourne, Victoria, Australia [3] Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia.

Background: The aims of the present study were (i) to characterize the relationship between mean airway pressure (PAW) and reactance measured at 5 Hz (reactance of the respiratory system (X RS), forced oscillation technique) and (ii) to compare optimal PAW (P opt) defined by X RS, oxygenation, lung volume (VL), and tidal volume (VT) in preterm lambs receiving high-frequency oscillatory ventilation (HFOV).

Methods: Nine 132-d gestation lambs were commenced on HFOV at PAW of 14 cmH2O (P start). PAW was increased stepwise to a maximum pressure (P max) and subsequently sequentially decreased to the closing pressure (Pcl, oxygenation deteriorated) or a minimum of 6 cmH2O, using an oxygenation-based recruitment maneuver. X RS, regional V L (electrical impedance tomography), and V T were measured immediately after (t 0 min) and 2 min after (t 2 min) each PAW decrement. P opt defined by oxygenation, X RS, V L, and V T were determined.

Results: The PAW-X RS and PAW-VT relationships were dome shaped with a maximum at Pcl+6 cmH2O, the same point as P opt defined by VL. Below Pcl+6 cmH2O, X RS became unstable between t 0 min and t 2 min and was associated with derecruitment in the dependent lung. P opt, as defined by oxygenation, was lower than the P opt defined by X RS, V L, or V T.

Conclusion: X RS has the potential as a bedside tool for optimizing PAW during HFOV.
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http://dx.doi.org/10.1038/pr.2013.251DOI Listing
April 2014

Surfactant before the first inflation at birth improves spatial distribution of ventilation and reduces lung injury in preterm lambs.

J Appl Physiol (1985) 2014 Feb 19;116(3):251-8. Epub 2013 Dec 19.

Neonatal Research, Murdoch Childrens Research Institute, Parkville, Australia;

The interrelationship between the role of surfactant and a sustained inflation (SI) to aid ex utero transition of the preterm lung is unknown. We compared the effect of surfactant administered before and after an initial SI on gas exchange, lung mechanics, spatial distribution of ventilation, and lung injury in preterm lambs. Gestational-age lambs (127 days; 9 per group) received 100 mg/kg of a surfactant (Curosurf) either prior (Surf+SI) or 10 min after birth (SI+Surf). At birth, a 20-s, 35 cmH2O SI was applied, followed by 70 min of positive pressure ventilation. Oxygenation, carbon dioxide removal, respiratory system compliance, end-expiratory thoracic volume (via respiratory inductive plethysmography), and distribution of end-expiratory volume and ventilation (via electrical impedance tomography) were measured throughout. Early markers of lung injury were analyzed using quantitative RT-PCR. During the first 15 min, oxygenation, carbon dioxide removal, and compliance were better in the Surf+SI group (all P < 0.05). End-expiratory volume on completion of the sustained inflation was higher in the Surf+SI group than the SI+Surf group; 11 ± 1 ml/kg vs. 7 ± 1 ml/kg (mean ± SE) (P = 0.043; t-test), but was not different at later time points. Although neither achieved homogenous aeration, spatial ventilation was more uniform in the Surf+SI group throughout; 50.1 ± 10.9% of total ventilation in the left hemithorax at 70 min vs. 42.6 ± 11.1% in the SI+Surf group. Surf+SI resulted in lower mRNA levels of CYR61 and EGR1 compared with SI+Surf (P < 0.001, one-way ANOVA). Surfactant status of the fetal preterm lung at birth influences the mechanical and injury response to a sustained inflation and ventilation by changing surface tension of the air/fluid interface.
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http://dx.doi.org/10.1152/japplphysiol.01142.2013DOI Listing
February 2014

Effect of sustained inflation vs. stepwise PEEP strategy at birth on gas exchange and lung mechanics in preterm lambs.

Pediatr Res 2014 Feb 20;75(2):288-94. Epub 2013 Nov 20.

1] Neonatal Research, Murdoch Childrens Research Institute, Parkville, Australia [2] Neonatal Research, The Royal Women's Hospital, Parkville, Australia [3] Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Australia.

Background: Sustained inflation (SI) at birth facilitates establishment of functional residual capacity (FRC) in the preterm lung, but the ideal lung recruitment strategy is unclear. We have compared the effect of SI and a stepwise positive end-expiratory pressure (PEEP; SEP) strategy in a preterm model.

Methods: 127 d gestation lambs received either 20-s SI (n = 9) or 2 cmH2O stepwise PEEP increases to 20 cmH2O every 10 inflations, and then decreases to 6 cmH2O (n = 10). Ventilation continued for 70 min, with surfactant administered at 10 min. Alveolar-arterial oxygen gradient (AaDO2), compliance (C(dyn)), end-expiratory thoracic volume (EEVRIP; respiratory inductive plethysmography), and EEV and C(dyn) in the gravity-dependent and nondependent hemithoraces (electrical impedance tomography) were measured throughout. Early mRNA markers of lung injury were analyzed using quantitative real-time PCR.

Results: From 15 min of life, AaDO2 was lower in SEP group (P < 0.005; two-way ANOVA). SEP resulted in higher and more homogeneous C(dyn) (P < 0.0001). Mean (SD) EEVRIP at 5 min was 18 (9) ml/kg and 6 (5) ml/kg following SEP and SI, respectively (P = 0.021; Bonferroni posttest); this difference was due to a greater nondependent hemithorax EEV. There was no difference in markers of lung injury.

Conclusion: An SEP at birth improved gas exchange, lung mechanics, and EEV, without increasing lung injury, compared to the SI strategy used.
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http://dx.doi.org/10.1038/pr.2013.218DOI Listing
February 2014

The stable microbubble test for determining continuous positive airway pressure (CPAP) success in very preterm infants receiving nasal CPAP from birth.

Neonatology 2013 17;104(3):188-93. Epub 2013 Aug 17.

Newborn Research, The Royal Women's Hospital, Melbourne, Vic., Australia.

Background: Very preterm infants can be treated with nasal continuous positive airway pressure (CPAP) from birth, but some fail. A rapid test, such as the stable microbubble test (SMT) on gastric aspirate, may identify those who can be managed successfully using CPAP.

Objective: To determine if SMT can identify soon after birth, very preterm infants who may be successfully managed on CPAP alone.

Methods: Stable microbubbles (diameter <15 µm) were counted in gastric aspirates taken <1 h of age from infants <30 weeks' gestation, who received CPAP from birth. Infants failed CPAP if intubated at <72 h of age. Clinicians were masked to SMT results. A receiver operating characteristic curve was generated to determine the relationship between number of microbubbles/mm(2) and subsequent intubation.

Results: 68 infants of mean (SD) 28.1 (1.4) weeks' gestation received CPAP in the delivery room at a median (interquartile range) pressure 7 (6-8) cmH2O and FiO2 0.25 (0.21-0.3). Gastric aspirates were taken at a median (interquartile range) age of 0.5 (0.3-0.6) hours. The best cut-off point for predicting CPAP success or failure was a SMT count of 8 microbubbles/mm(2). The area under the receiver operating characteristic curve was 0.8 (95% CI 0.7-0.9). A SMT count ≥8 microbubbles/mm(2) had a sensitivity of 53%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 60% for predicting CPAP success.

Conclusion: Infants treated with CPAP from birth, who had SMT counts ≥8 microbubbles/mm(2) on their gastric aspirate, did not fail CPAP.
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http://dx.doi.org/10.1159/000353363DOI Listing
July 2014

A comparison of different bedside techniques to determine endotracheal tube position in a neonatal piglet model.

Pediatr Pulmonol 2013 Feb 21;48(2):138-45. Epub 2012 May 21.

Neonatal Research, Murdoch Childrens Research Institute, Melbourne, Australia.

Rationale: Endotracheal tube (ETT) malposition is common and an increasing number of non-invasive techniques to aid rapid identification of tube position are available. Electrical impedance tomography (EIT) is advocated as a tool to monitor ventilation.

Objective: This study aimed to compare EIT with five other non-invasive techniques for identifying ETT position in a piglet model.

Methodology: Six saline lavage surfactant-depleted piglets were studied. Periods of ventilation with ETT placed in the oesophagus or a main bronchus (MB) were compared with an appropriately placed mid-tracheal ETT. Colorimetric end-tidal CO(2) (Pedi-Cap®), SpO(2) and heart rate, tidal volume (${\rm V}_{{\rm T}_{{\rm ao}} } $) using a hot-wire anemometer at the airway opening, tidal volume using respiratory inductive plethysmography (${\rm V}_{{\rm T}_{{\rm RIP}} } $) and regional tidal ventilation within each hemithorax (EIT) were measured.

Results: Oesophageal ventilation: Pedi-Cap® demonstrated absence of color change. ${\rm V}_{{\rm T}_{{\rm ao}} } $, ${\rm V}_{{\rm T}_{{\rm RIP}} } $, and EIT correctly demonstrated no tidal ventilation. SpO(2) decreased from mean (SD) 96 (2)% to 74 (12)% (P < 0.05; Bonferroni post-test), without heart rate change. MB ventilation: SpO(2) , heart rate and Pedi-Cap® were unchanged compared with mid-tracheal position. ${\rm V}_{{\rm T}_{{\rm ao}} } $ and ${\rm V}_{{\rm T}_{{\rm RIP}} } $ decreased from a mean (SD) 10.8 (5.6) ml/kg and 14.6 (6.2) ml/kg to 5.5 (1.9) ml/kg and 6.4 (2.6) ml/kg (both P < 0.05; Bonferroni post-test). EIT identified the side of MB ventilation, with a mean (SD) 95 (3)% reduction in tidal volume in the unventilated lung.

Conclusions: EIT not only correctly identified oesophageal ventilation but also localized the side of MB ventilation. At present, no one technique is without limitations and clinicians should utilize a combination in addition to clinical judgement.
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http://dx.doi.org/10.1002/ppul.22580DOI Listing
February 2013

Effect of closed endotracheal tube suction method, catheter size, and post-suction recruitment during high-frequency jet ventilation in an animal model.

Pediatr Pulmonol 2012 Aug 30;47(8):749-56. Epub 2012 Jan 30.

Neonatal Research, Murdoch Children's Research Institute, Melbourne, Victoria 3052, Australia.

Rationale: High-frequency jet ventilation (HFJV) is often used to treat infants with pathologies associated with gas trapping and abnormal lung mechanics, who are sensitive to the adverse effects of suction.

Objective: This study aimed to investigate the effect of closed suction (CS), catheter size, and the use of active post-suction sighs on tracheal pressure (P(trach)), and global and regional end-expiratory lung volume (EELV) during HFJV.

Methods: Six anaesthetized and muscle-relaxed adult rabbits were stabilized on HFJV. CS was performed using all permutations of three CS methods (Continual negative pressure, negative pressure applied during Withdrawal, and HFJV in Standby) and 6 French gauge (6 FG) and 8 French gauge (8 FG) catheter, randomly assigned. The sequence was repeated using post-suction sighs. P(trach), absolute (respiratory inductive plethysmography) and regional (electrical impedance tomography; expressed as percentage of vital capacity for the defined region of interest, %Z(VCroi) ) EELV were measured before, during and 60 sec post-suction.

Results: CS methods exerted no difference on ΔP(trach), ΔEELV(RIP), or Δ%Z(VCroi) . 8FG catheter resulted in a mean (95%CI) 20.0 (17.9,22.2) cm H(2)O greater loss of P(trach) during suction compared to 6FG (Bonferroni post-test). Mean (± SD) ΔEELV(RIP) was -6(±3) and -2(±1) ml/kg with the 8 and 6 FG catheters (P < 0.0001; Bonferroni post-test). ΔEELV was 31.7 (21.1,42.4) %Z(VCroi) and 24.8 (10.9,38.7) %Z(VCroi) greater in the ventral and dorsal hemithoraces using the 8 FG. Only after 8 FG CS was post-suction recruitment required to restore EELV.

Conclusions: In this animal model receiving HFJV, ΔP(trach), ΔEELV, and need for post-suction recruitment during CS were most influenced by catheter size. Volume changes within the lung were uniform.
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http://dx.doi.org/10.1002/ppul.21607DOI Listing
August 2012

Electrical impedance tomography can rapidly detect small pneumothoraces in surfactant-depleted piglets.

Intensive Care Med 2012 Feb 26;38(2):308-15. Epub 2011 Nov 26.

Neonatal Research, Murdoch Childrens Research Institute, Melbourne, Australia.

Purpose: Diagnosis of pneumothorax relies on clinical suspicion and chest X-ray, and is often delayed. We aimed to determine whether electrical impedance tomography (EIT) can accurately identify the presence of surgically created pneumothoraces before significant changes in clinical parameters.

Methods: Six anesthetized and muscle-relaxed piglets with surfactant-depleted lungs were studied. Following chest drain insertion into the right ventral chest, 10-20 ml aliquots of air were instilled into the pleural space to a maximum volume of 200 ml. The pneumothorax was drained by attaching a Heimlich valve to the chest drain. At each instillation and after draining the pneumothorax, global and regional end-expiratory intra-thoracic volumes (EEV) were measured using respiratory inductive plethysmography (RIP) and EIT concurrently with [Formula: see text], heart rate and blood pressure.

Results: A significantly greater change in both global EEV(RIP) and EEV within the right ventral quadrant was seen at all volume instillations, from as little as 10 ml, compared with all other quadrants. There was no difference in EEV within the left ventral and both dorsal quadrants. Sp(O)(2) fell below 90% at 100 ml instillation. Tachycardia occurred at 140 ml instillation. EIT identified a 60% resolution of pneumothoraces within 60 s of attachment of the Heimlich valve.

Conclusions: EIT accurately detects very small pneumothoraces before physiological parameters change.
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http://dx.doi.org/10.1007/s00134-011-2421-zDOI Listing
February 2012

Identification of pneumothorax in very preterm infants.

J Pediatr 2011 Jul 6;159(1):115-120.e1. Epub 2011 Feb 6.

Neonatal Services, The Royal Women's Hospital, Melbourne, Victoria, Australia.

Objective: To compare respiratory and other morbidities between very preterm infants with and without a pneumothorax and to determine whether infants at higher risk of pneumothorax can be identified early in their course.

Study Design: Preterm infants at 23 to 28 weeks' gestation with pneumothorax were compared with matched control subjects. Demographic and clinical data from birth through the first 72 hours were compared.

Results: Sixty-two (9.2%) of 675 infants had pneumothorax. There were no significant differences in the baseline maternal and infant characteristics. Mortality was significantly higher in the pneumothorax group (43%) versus control subjects (13%). There was no significant difference in continuous positive airway pressure or surfactant treatment or rates of intraventricular hemorrhage or bronchopulmonary dysplasia. Infants treated with early continuous positive airway pressure in the delivery room typically had pneumothorax on day 2 of life. Those who had pneumothorax had higher inspired fraction of oxygen before its diagnosis and over the first 12 hours of life than did control subjects.

Conclusions: Pneumothorax is associated with increased mortality and with severity of lung disease in the first day of life. It may be possible to identify babies at highest risk of pneumothorax on the basis of inspired fraction of oxygen in the first 12 hours of life.
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http://dx.doi.org/10.1016/j.jpeds.2010.12.016DOI Listing
July 2011
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