Review finds insufficient evidence to support the routine use of heated, humidified high-flow nasal cannula use in neonates.

UNLABELLED: A literature review was carried out following concerns about the use of heated, humidified, high-flow nasal cannulae (HHFNC) in premature infants. Randomised trials following extubation showed that HHFNC was associated with similar or greater reintubation rates than nasal continuous positive airway pressure, but significantly better nasal trauma scores. Infections with Ralstonia bacteria were an issue. CONCLUSION: There is insufficient evidence to support the routine use of HHFNC for premature infants and further research is required.

Predictors of neonatal morbidity in fetuses with severe isolated congenital diaphragmatic hernia undergoing fetoscopic tracheal occlusion.

OBJECTIVES: To investigate neonatal morbidity in fetuses with severe congenital diaphragmatic hernia (CDH) treated with fetoscopic endoluminal tracheal occlusion (FETO) and compare it with historical controls with less severe forms of CDH that were managed expectantly. METHODS: This was a prospective, multicenter study on neonatal outcomes and prenatal predictors in 90 FETO survivors (78 left-sided, 12 right) and 41 controls from the antenatal CDH registry with either severe or moderate hypoplasia who were managed expectantly. We also investigated early neonatal morbidity indicators, including the need for patch repair, duration of mechanical ventilation and supplemental oxygen, age at full enteral feeding and incidence of pulmonary hypertension. RESULTS: Gestational age at delivery was predictive of duration of assisted ventilation (P = 0.046), days on supplemental oxygen (P = 0.019) and age at full enteral feeding (P = 0.020). When delivery took place after 34 weeks' gestation, neonatal morbidity of FETO cases was comparable with that of expectantly managed cases with moderate hypoplasia. CONCLUSIONS: Fetal intervention for severe CDH is associated with neonatal morbidity that is comparable with that of an expectantly managed group with less severe disease.

Antenatal and postnatal management of congenital cystic adenomatoid malformation.

Congenital thoracic malformations (CTMs) are a heterogeneous group of rare disorders that may involve the airways or lung parenchyma. The authors have focused on the condition that causes the most controversy, namely, congenital cystic adenomatoid malformation (CCAM). The reported incidence is 3.5 and 0.94 per 10,000 live births for CTMs and CCAMs respectively. Ultrasound is the antenatal imaging modality of choice for screening for CCAMs whilst magnetic resonance imaging is complimentary for morphological and volumetric evaluation of the foetal lung. Most CCAMs are detected antenatally with only a small proportion presenting postnatally. Only a few CCAMs cause foetal problems, with foetal hydrops being the best predictor of death. Although many CCAMs regress during pregnancy, most remain detectable postnatally by CT scans. Surgical excision of symptomatic lesions is relatively straightforward, but management of asymptomatic lesions is controversial. Some surgeons adopt a "wait and see" approach operating only on those patients who develop symptoms, but others operate on asymptomatic patients usually within the first year of life. Due to the potential of malignant transformation, children should have long term follow up. There is an urgent need to delineate the natural history of antenatally detected CCAMs to guide future management.

Congenital diaphragmatic hernia.

Infants with congenital diaphragmatic hernia (CDH) have significant mortality and long-term morbidity. Only 60-70% survive and usually those in high-volume centres. The current Task Force, therefore, has convened experts to evaluate the current literature and make recommendations on both the antenatal and post-natal management of CDH. The incidence of CDH varies from 1.7 to 5.7 per 10,000 live-born infants depending on the study population. Antenatal ultrasound scanning is routine and increasingly complemented by the use of magnetic resonance imaging. For isolated CDH, antenatal interventions should be considered, but the techniques need vigorous evaluation. After birth, management protocols are often used and have improved outcome in nonrandomised studies, but immediate intubation at birth and gentle ventilation are important. Pulmonary hypertension is common and its optimal management is crucial as its severity predicts the outcome. Usually, surgery is delayed to allow optimal medical stabilisation. The role of minimal invasive post-natal surgery remains to be further defined. There are differences in opinion about whether extracorporeal membrane oxygenation improves outcome. Survivors of CDH can have a high incidence of comorbidities; thus, multidisciplinary follow-up is recommended. Multicentre international trials are necessary to optimise the antenatal and post-natal management of CDH patients.

Three-dimensional ultrasound fetal lung volumes and infant respiratory outcome: a prospective observational study.

OBJECTIVE: To determine if fetal lung volumes (FLVs), determined by three-dimensional rotational ultrasound and virtual organ computer-aided analysis software (vocal), correlated with neonatal respiratory outcomes in surviving infants who had a high risk [fetuses with congenital diaphragmatic hernia (CDH)], lower risk [fetuses with anterior wall defects (AWDs)] and no risk (controls) of abnormal antenatal lung growth. DESIGN: Prospective observational study. SETTING: Tertiary fetal medicine and neonatal intensive care units. POPULATION: Sixty fetuses (25 with CDH, 25 with AWDs and ten controls). METHODS: FLVs were measured and expressed as the percentage of the observed compared with the expected for gestational age. MAIN OUTCOME MEASURES: Neonatal respiratory outcome was determined by the duration of supplemental oxygen, mechanical ventilation and dependencies, and assessment of lung volume using a gas dilution technique to measure functional residual capacity (FRC). RESULTS: The infants with CDH had lower FLV results than both the infants with AWDs (P=0.05) and the controls (P<0.05). The infants with CDH had longer durations of mechanical ventilation (P<0.001) and supplementary oxygen (P<0.001) dependence, compared with infants with AWDs. The infants with CDH had a lower median FRC than both the infants with AWDs (P<0.001) and the controls (P<0.001). FLV results correlated significantly with the durations of dependency on ventilation (r= -0.744, P<0.01) and oxygen (r= -0.788, P<0.001), and with FRC results (r=0.429, P=0.001). CONCLUSIONS: These results suggest that FLVs obtained using three-dimensional rotational ultrasound might be useful in predicting neonatal respiratory outcome in surviving infants who had varying risks of abnormal lung growth. Larger and more comprehensive studies are needed to clarify the role that lung volume measurements have in assessing lung function and growth.

Diaphragm electromyogram in infants with abdominal wall defects and congenital diaphragmatic hernia.

Measurement of the diaphragm electromyogram (EMGdi) elicited by phrenic nerve stimulation could be useful to assess neonates suffering from respiratory distress due to diaphragm dysfunction, as observed in infants with abdominal wall defects (AWD) or congenital diaphragmatic hernia (CDH). The study aims were to assess the feasibility of recording EMGdi using a multipair oesophageal electrode catheter and examine whether diaphragm muscle and/or phrenic nerve function was compromised in AWD or CDH infants. Diaphragm compound muscle action potentials elicited by magnetic phrenic nerve stimulation were recorded from 18 infants with surgically repaired AWD (n = 13) or CDH (n = 5), median (range) gestational age 36.5 (34-40) weeks. Diaphragm strength was assessed as twitch transdiaphragmatic pressure (TwP(di)). One AWD patient had prolonged phrenic nerve latency (PNL) bilaterally (left 9.31 ms, right 9.49 ms) and two CDH patients had prolonged PNL on the affected side (10.1 ms and 10.08 ms). There was no difference in left and right TwP(di) in either group. PNL correlated significantly with TwP(di) in CDH (r = 0.8; p = 0.009). Oesophageal EMG and magnetic stimulation of the phrenic nerves can be useful to assess phrenic nerve function in infants. Reduced phrenic nerve conduction accompanies the reduced diaphragm force production observed in infants with CDH.

Standardized postnatal management of infants with congenital diaphragmatic hernia in Europe: the CDH EURO Consortium consensus.

Congenital diaphragmatic hernia (CDH) is associated with high mortality and morbidity. To date, there are no standardized protocols for the treatment of infants with this anomaly. However, protocols based on the literature and expert opinion might improve outcome. This paper is a consensus statement from the CDH EURO Consortium prepared with the aim of achieving standardized postnatal treatment in European countries. During a consensus meeting between high-volume centers with expertise in the treatment of CDH in Europe (CDH EURO Consortium), the most recent literature on CDH was discussed. Thereafter, 5 experts graded the studies according to the Scottish Intercollegiate Guidelines Network (SIGN) Criteria. Differences in opinion were discussed until full consensus was reached. The final consensus statement, therefore, represents the opinion of all consortium members. Multicenter randomized controlled trials on CDH are lacking. Use of a standardized protocol, however, may contribute to more valid comparisons of patient data in multicenter studies and identification of areas for further research.

Medicines used in respiratory diseases only seen in children.

Detailed literature searches were carried out in seven respiratory disease areas. Therapeutic evidence for efficacy of medicinal products was assessed using the Grades of Recommendation, Assessment and Evaluation (GRADE) methodology, as well as an assessment of safety and side-effects. Systemic corticosteroids may reduce the development of bronchopulmonary dysplasia but have serious side-effects. Antioxidants need further study to demonstrate whether they have long-term benefits. Treatments for acute bronchiolitis have shown little benefit but new antiviral and monoclonal antibodies need further assessment. Well-constructed studies are needed to confirm the value of inhaled corticosteroids and/or montelukast in the management of viral-induced wheeze. Corticosteroids are the treatment of choice in croup. Minimal or no information is available for the treatment of congenital lung abnormalities, bronchiolitis obliterans and interstitial lung disease.

Relation of exhaled nitric oxide levels to development of bronchopulmonary dysplasia.

OBJECTIVE: To test the hypothesis that exhaled nitric oxide levels on day 28 and changes in exhaled nitric oxide levels in the neonatal period would differ according to whether infants developed bronchopulmonary dysplasia (BPD) and its severity. DESIGN: Prospective observational study. SETTING: Tertiary neonatal intensive care unit. PATIENTS: 80 infants (median gestational age 28, range 24-32 weeks), 46 of whom developed BPD. INTERVENTIONS: Exhaled nitric oxide measurements were attempted on days 3, 5, 7, 14, 21 and 28. MAIN OUTCOME MEASURES: BPD (oxygen dependency at 28 days), mild BPD (oxygen dependent at 28 days, but not 36 weeks postmenstrual age (PMA)); moderate BPD (oxygen dependent at 36 weeks PMA) and severe BPD (respiratory support dependent at 36 weeks PMA). RESULTS: On day 28, exhaled nitric oxide levels were higher in infants with BPD compared to those without BPD (p<0.001) and there was a linear trend in exhaled nitric oxide results as BPD severity increased (p = 0.006). No significances in the change in exhaled nitric oxide levels over the neonatal period were found between the four groups. CONCLUSION: Exhaled nitric oxide levels are raised in infants with established BPD, particularly in those developing moderate or severe BPD, and may reflect ongoing inflammation.

Work of breathing during SIMV with and without pressure support.

OBJECTIVE: In a randomised trial, pressure support with synchronised intermittent mandatory ventilation (SIMV) compared to SIMV alone was associated with a significant reduction in supplementary oxygen duration. The hypothesis that the addition of pressure support to SIMV compared to SIMV alone would reduce the work of breathing was examined. DESIGN: Prospective study. SETTING: Perinatal service. PATIENTS: 20 infants, with a mean gestational age of 31 weeks, being weaned from mechanical ventilation were studied. INTERVENTIONS: 1 h periods of SIMV and SIMV with pressure support at 50% of the difference between the peak inflating pressure and positive end expiratory pressures. MAIN OUTCOME MEASURES: The work of breathing was assessed by measurement of the transdiaphragmatic pressure time product (PTPdi). RESULTS: The mean PTPdi on SIMV plus pressure support was 112 cm H(2)Oxs/min, approximately 20% lower than that on SIMV alone (141 cm H(2)Oxs/min) (p<0.001). CONCLUSION: The addition of pressure support to SIMV reduces the work of breathing in infants being weaned from the ventilator.

School age outcome of hospitalisation with respiratory syncytial virus infection of prematurely born infants.

BACKGROUND: Hospitalisation due to respiratory syncytial virus (RSV) infection in the first 2 years after birth has been associated with increased healthcare utilisation and associated costs up to 5 years of age in children born prematurely at less than 32 weeks of gestation who developed bronchopulmonary dysplasia (BPD). A study was undertaken to determine whether hospitalisation due to RSV infection in the first 2 years was associated with increased morbidity and lung function abnormalities in such children at school age, and if any effects were influenced by age. METHODS: Healthcare utilisation and cost of care in years 5-7 were reviewed in 147 children and changes in healthcare utilisation between 0 and 8 years were assessed also using results from two previous studies. At age 8-10 years, 77 children had their lung function assessed and bronchial hyper-responsiveness determined. RESULTS: Children hospitalised with RSV infection (n = 25) in the first 2 years had a greater cost of care related to outpatient attendance than those with a non-respiratory or no admission (n = 72) when aged 5-7 years (p = 0.008). At 8-10 years of age, children hospitalised with RSV infection (n = 14) had lower forced expiratory volume in 0.75 s (FEV(0.75)) (p = 0.015), FEV(0.75)/forced vital capacity (p = 0.027) and flows at 50% (p = 0.034) and 75% (p = 0.006) of vital capacity than children hospitalised for non-RSV causes (n = 63). Healthcare utilisation decreased with increasing age regardless of RSV hospitalisation status. CONCLUSIONS: In prematurely born children who had BPD, hospitalisation due to RSV infection in the first 2 years is associated with reduced airway calibre at school age.

Sleeping position, oxygenation and lung function in prematurely born infants studied post term.

OBJECTIVE: To determine the effect of sleeping position on the lung function of prematurely born infants when post term, whether any effect was similar to that before discharge from the neonatal unit, and if it differed according to bronchopulmonary (BPD) status. DESIGN: Prospective study. SETTING: Tertiary neonatal unit. PATIENTS: Twenty infants, median gestational age 30 weeks (range 25-32); 10 had BPD. INTERVENTIONS: Before neonatal unit discharge (median age 36 weeks postmenstrual age (PMA)) and when post term, infants were studied prone and supine, each position maintained for 3 h. MAIN OUTCOME MEASURES: Oxygen saturation was monitored continuously and, at the end of each 3 h period, functional residual capacity (FRC) and compliance (CRS) and resistance (RRS) of the respiratory system were measured. RESULTS: At a median of 36 weeks PMA and 6 weeks later (post term), respectively, oxygen saturation (98% vs 96%, p = 0.001; 98% vs 97%, p = 0.011), FRC (26 vs 24 ml/kg, p<0.0001; 35 vs 31 ml/kg, p = 0.001) and CRS (3.0 vs 2.4 ml/cm H(2)O, p = 0.034; 3.7 vs 2.5 ml/cm H(2)O, p = 0.015) were higher in the prone than the supine position. In the prone position, both BPD and non-BPD infants had significantly greater FRCs on both occasions and oxygen saturation at 36 weeks PMA, but oxygen saturation was significantly better post term only in non-BPD infants. Twelve infants had superior oxygen saturation and 17 superior FRCs in the prone compared with the supine position at both 36 weeks PMA and post term. CONCLUSIONS: These results suggest that lung function impairment does not explain why prematurely born infants are at increased risk of sudden infant death syndrome in the prone compared with the supine position.

Prenatal prediction of neonatal morbidity in survivors with congenital diaphragmatic hernia: a multicenter study.

OBJECTIVES: To investigate the value of the observed to expected fetal lung area to head circumference ratio (o/e LHR) and liver position in the prediction of neonatal morbidity in survivors with congenital diaphragmatic hernia (CDH). METHODS: Neonatal morbidity was recorded in 100 consecutive cases with isolated CDH diagnosed in fetal medicine units, which were expectantly managed in the prenatal period, were delivered after 30 weeks and survived until discharge from hospital. Regression analysis was used to identify the significant predictors of morbidity, including prenatal and immediate neonatal findings. RESULTS: The o/e LHR provided significant prediction of the need for prosthetic patch repair, duration of assisted ventilation, need for supplemental oxygen at 28 days, and incidence of feeding problems. An additional independent prenatal predictor of the need for patch repair was the presence of fetal liver in the chest. CONCLUSIONS: In isolated CDH the prenatally assessed size of the contralateral lung is a significant predictor of the need for prosthetic patch repair, the functional consequences of impaired lung development and occurrence of feeding problems.

Does nasal CPAP reduce bronchopulmonary dysplasia (BPD)?

UNLABELLED: Early nasal continuous positive airway pressure (nCPAP) or early surfactant therapy with early extubation onto nCPAP rather than continued mechanical ventilation has been adopted by many centres, particularly in Scandinavia, as part of the treatment of newborns with respiratory distress syndrome. It has been suggested that bronchopulmonary dysplasia is less of a problem in centres adopting such a policy. Results from randomized trials suggest prophylactic or early nCPAP may reduce bronchopulmonary dysplasia (BPD), but further studies are required to determine the relative contributions of an early lung recruitment policy, early surfactant administration and nCPAP in reducing BPD. In addition, the optimum method of generating and delivering CPAP needs to be determined. CONCLUSION: The efficacy of nCPAP in improving long-term respiratory outcomes needs to be compared with the newer ventilator techniques with the optimum and timing of delivery of surfactant administration.

Synchronized mechanical ventilation for respiratory support in newborn infants.

BACKGROUND: During synchronized mechanical ventilation, positive airway pressure and spontaneous inspiration coincide. If synchronous ventilation is provoked, adequate gas exchange should be achieved at lower peak airway pressures, potentially reducing baro/volutrauma, air leak and bronchopulmonary dysplasia. Synchronous ventilation can potentially be achieved by manipulation of rate and inspiratory time during conventional ventilation and employment of patient triggered ventilation. OBJECTIVES: To compare the efficacy of: (i) synchronized mechanical ventilation, delivered as high frequency positive pressure ventilation (HFPPV) or patient triggered ventilation - assist control ventilation (ACV) or synchronous intermittent mandatory ventilation (SIMV)) with conventional ventilation (CMV) (ii) different types of triggered ventilation (ACV, SIMV, pressure regulated volume control ventilation (PRVCV) and SIMV plus pressure support (PS) SEARCH STRATEGY: Searches from 1985-2007 of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2007),Oxford Database of Perinatal Trials, MEDLINE, previous reviews, abstracts and symposia proceedings; hand searches of journals in the English language and contact with expert informants. SELECTION CRITERIA: Randomised or quasi-randomised clinical trials comparing synchronized ventilation delivered as high frequency positive pressure ventilation (HFPPV) or triggered ventilation (ACV/SIMV) to conventional mechanical ventilation (CMV) in neonates. Randomised trials comparing different triggered ventilation modes (ACV, SIMV, SIMV plus PS and PRVCV) in neonates. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including mortality, air leaks (pneumothorax or pulmonary interstitial emphysema (PIE)), severe intraventricular haemorrhage (grades 3 and 4), bronchopulmonary dysplasia (BPD) (oxygen dependency beyond 28 days), moderate/severe BPD (oxygen/respiratory support dependency beyond 36 weeks postmenstrual age (PMA) and duration of weaning/ventilation. Four comparisons were made: (i) HFPPV vs. CMV; (ii) ACV/SIMV vs. CMV; (iii) ACV vs. SIMV or PRVCV vs. SIMV (iv) SIMV plus PS vs. SIMV. Data analysis was conducted using relative risk for categorical outcomes, weighted mean difference for outcomes measured on a continuous scale. MAIN RESULTS: Fourteen studies were eligible for inclusion. The meta-analysis demonstrates that HFPPV compared to CMV was associated with a reduction in the risk of air leak (typical relative risk for pneumothorax was 0.69, 95% CI 0.51, 0.93). ACV/SIMV compared to CMV was associated with a shorter duration of ventilation (weighted mean difference -34.8 hours, 95% CI -62.1, -7.4). ACV compared to SIMV was associated with a trend to a shorter duration of weaning (weighted mean difference -42.4 hours, 95% CI -94.4, 9.6). Neither HFPPV nor triggered ventilation was associated with a significant reduction in the incidence of BPD. There was a non-significant trend towards a lower mortality rate using HFPPV vs. CMV and a non-significant trend towards a higher mortality rate using triggered ventilation vs. CMV. No disadvantage of HFPPV or triggered ventilation was noted regarding other outcomes. Since the last review, two new patient triggered modes have been included: pressure regulated volume control ventilation (PRVCV) and SIMV plus pressure support. Each of these methods of ventilation has only been tested in single randomised trials with no significant advantages in important outcomes. AUTHORS' CONCLUSIONS: Compared to conventional ventilation, benefit is demonstrated for both HFPPV and triggered ventilation with regard to a reduction in air leak and a shorter duration of ventilation, respectively. In none of the trials was complex respiratory monitoring undertaken and thus it is not possible to conclude that the mechanism of producing those benefits is by provocation of synchronized ventilation. Further trials are needed to determine whether synchronized ventilation is associated with other benefits, but optimisation of trigger and ventilator design with respect to respiratory diagnosis is encouraged before embarking on further trials. It is essential newer forms of triggered ventilation are tested in adequately powered randomised trials with long-term outcomes before they are incorporated into routine clinical practice.

Difficult extubation in low birthweight infants.

Randomised trials have demonstrated that ventilation techniques which support every spontaneous breath are the most efficacious weaning modes. Nasal continuous positive airway pressure after extubation reduces the likelihood of incidents leading to the need for reintubation in very low birthweight infants; further work is needed to determine if there are advantages of particular delivery techniques. Both methylxanthines and dexamethasone facilitate weaning and extubation; the efficacy of low-dose dexamethasone merits further investigation. Assessments of the efficacy of respiratory efforts and hence the balance of respiratory drive, muscle performance and respiratory load appear to best predict weaning and extubation success. Essential to the success of weaning and extubation are dedicated staff, whether this will be assisted by computerised decision-making tools requires testing. The above approaches are not mutually exclusive and those indicated by this review as appropriately evidence based should be considered by practitioners for current use to reduce difficult/unsuccessful extubation.

Peak expiratory flow in Afro-Caribbean children with and without sickle cell anaemia.

AIMS: To create a reference range of peak expiratory flow (PEF) results of Afro-Caribbean children and determine whether interpretation of PEF results in children with sickle cell anaemia (SCA) differed according to whether comparison was made of results obtained from children of similar age or height. METHODS: A prospective observational study was carried out in two specialist sickle cell disease clinics. Seventy-eight nonasthmatic African and Caribbean (AC) controls (age range 2.6-17.8 years), and 99 nonasthmatic SCA children (age range 3.4-17.3 years) were recruited. PEF was measured using a dry rolling sealed spirometer before and after bronchodilator therapy. RESULTS: PEF results in the AC controls correlated with height (r = 0.88, p< 0.0001). Comparison of similarly aged children demonstrated that pre- (p = 0.02) and post- (p = 0.04) bronchodilator PEF results were lower in the SCA children, but comparison of children of similar height revealed no statistically significant differences in PEF results between children with SCA and controls. The SCA children tended to be shorter than the controls. CONCLUSION: The results suggest PEF measurements are not a useful method of monitoring the respiratory status of children with sickle cell disease.

Benefit of preformed silos in the management of gastroschisis.

Gastroschisis is traditionally managed by primary closure (PC) or delayed closure after surgical silo placement. Bedside insertion of preformed silos (PFS) and delayed closure has become more widespread, although its benefits remain unclear. To identify differences in outcome of infants managed with PFS compared with traditional closure (TC) techniques. Single-centre retrospective review of 53 consecutive neonates admitted between February 2000 and January 2006. Data expressed as median (range). Non-parametric statistical analysis used with P < 0.05 regarded as significant. Forty infants underwent TC and 13 had PFS and delayed closure. Median ventilation time in both groups was 4 days (P = 0.19) however this was achieved with higher mean airway pressures (MAPs) (day 0, 10 (5-16) versus 8 (5-10) cmH(2)O; P = 0.02) and inspired oxygen (40 (21-100) versus 30 (21-60)%; P = 0.03) in TC group. Urine output on day-1 of life was significantly higher in PFS group (1.1 (0.16-3.07) versus 0.45 (0-2.8) ml/kg/h; P = 0.02). Inotrope support was required in 17/40 (43%) of TC versus 0/13 (0%) in PFS (P < 0.01). After exclusion of infants with short bowel syndrome and/or intestinal atresia (n = 9), there was a shorter time to full enteral feeds in the TC group (22 (12-36) versus 27 (17-45); P = 0.07), although there was no difference in the period of parenteral nutrition (PN) (P = 0.1) or overall hospital stay (P = 0.34). No deaths or episodes of necrotizing enterocolitis occurred. The use of PFS for gastroschisis closure is associated with a reduction in pulmonary barotrauma, better tissue perfusion and improved early renal function, consistent with a reduction in abdominal compartment syndrome.