Lung ultrasound of the dependent lung detects real-time changes in lung volume in the preterm lamb.

BACKGROUND: Effective lung protective ventilation requires reliable, real-time estimation of lung volume at the bedside. Neonatal clinicians lack a readily available imaging tool for this purpose. OBJECTIVE: To determine the ability of lung ultrasound (LUS) of the dependent region to detect real-time changes in lung volume, identify opening and closing pressures of the lung, and detect pulmonary hysteresis. METHODS: LUS was performed on preterm lambs (n=20) during in vivo mapping of the pressure-volume relationship of the respiratory system using the super-syringe method. Electrical impedance tomography was used to derive regional lung volumes. Images were blindly graded using an expanded scoring system. The scores were compared with total and regional lung volumes, and differences in LUS scores between pressure increments were calculated. RESULTS: Changes in LUS scores correlated moderately with changes in total lung volume (r=0.56, 95% CI 0.47-0.64, p<0.0001) and fairly with right whole (r=0.41, CI 0.30-0.51, p<0.0001), ventral (r=0.39, CI 0.28-0.49, p<0.0001), central (r=0.41, CI 0.31-0.52, p<0.0001) and dorsal (r=0.38, CI 0.27-0.49, p<0.0001) regional lung volumes. The pressure-volume relationship of the lung exhibited hysteresis in all lambs. LUS was able to detect hysteresis in 17 (85%) lambs. The greatest changes in LUS scores occurred at the opening and closing pressures. CONCLUSION: LUS was able to detect large changes in total and regional lung volume in real time and correctly identified opening and closing pressures but lacked the precision to detect small changes in lung volume. Further work is needed to improve precision prior to translation to clinical practice.

Ultrasound Measurements of Intracranial Structures in Growth-Restricted Neonates with Fetal Blood Flow Redistribution: A Pilot Observational Study.

BACKGROUND: Fetal growth restriction (FGR) is associated with neonatal and long-term neuro-morbidity. Preferential redistribution of blood flow to the brain is a common antenatal adaptation in FGR. The impact of this "brain sparing," which may signify severity of FGR, on the growth of brain structures has not been studied. AIM: To compare corpus callosum (CC), cerebellar, and ventricular measurements of FGR neonates with evidence of fetal blood flow redistribution with those of gestation-matched appropriately grown (AGA) neonates. METHODS: This was a pilot, prospective observational study conducted at a tertiary level neonatal unit in Melbourne, Australia. Cranial ultrasound was done between days 1 and 3 of life in FGR and AGA neonates. RESULTS: Cranial ultrasound on 20 FGR, gestation (mean ± SD) 31.4 ± 3.1 weeks, weight 1,205 ± 463 g, and 20 AGA neonates, 31.1 ± 3.0 weeks, 1,668 ± 490 g, was performed. CC length was significantly decreased in FGR neonates as compared to AGA neonates (35.28 ± 3.47 vs. 38.83 ± 4.05 mm, p = 0.0002). CC was significantly thinner at genu (3.36 ± 0.66 vs. 4.04 ± 0.83 mm, p = 0.007), body (1.97 ± 0.36 vs. 2.27 ± 0.39 mm, p = 0.02), and splenium (4.07 ± 0.76 vs. 4.72 ± 0.75 mm, p = 0.003) in FGR vs. AGA neonates. CC-fastigium length was also significantly decreased (39.65 ± 3.87 vs. 41.96 ± 4.50 mm, p = 0.04). Similarly, FGR neonates showed decreased transverse cerebellar diameter (36.15 ± 5.51 vs. 38.81 ± 7.21 mm, p = 0.02), but ventricular measurements were comparable. In multivariate analysis, these differences were evident independent of the birth weight. CONCLUSIONS: CC and cerebellar measurements are significantly smaller in FGR neonates with fetal blood flow redistribution, which warrants further study.

Induction of left ventricular hypoplasia by occluding the foramen ovale in the fetal lamb.

Disturbed fetal haemodynamics often affects cardiac development and leads to congenital cardiac defects. Reduced left ventricular (LV) preload in the fetus may result in hypoplastic LV, mitral and aortic valve, mimicking a moderate form of hypoplastic left heart complex. We aimed to induce LV hypoplasia by occluding the foramen ovale (FO) to reduce LV preload in the fetal sheep heart, using percutaneous trans-hepatic catheterisation. Under maternal anaesthesia and ultrasound guidance, hepatic venous puncture was performed in six fetal lambs (0.7-0.75 gestation). A coronary guidewire was advanced into the fetal inferior vena cava, right and left atrium. A self-expandable stent was positioned across the FO. An Amplatzer Duct Occluder was anchored within the stent for FO occlusion. Euthanasia and post-mortem examination was performed after 3 weeks. Nine fetuses were used as age-matched controls. Morphometric measurements and cardiac histopathology were performed. Compared with controls, fetal hearts with occluded FO had smaller LV chamber, smaller mitral and aortic valves, lower LV-to-RV ratio in ventricular weight and wall volume, and lower number of LV cardiomyocyte nuclei. We conclude that fetal FO occlusion leads to a phenotype simulating LV hypoplasia. This large animal model may be useful for understanding and devising therapies for LV hypoplasia.

Stopping enteral feeds for prevention of transfusion-associated necrotising enterocolitis in preterm infants.

BACKGROUND: Feeding practices around the time of packed red blood cell transfusion have been implicated in the subsequent development of necrotising enterocolitis (NEC) in preterm infants. Specifically, it has been suggested that withholding feeds around the time of transfusion may reduce the risk of subsequent NEC. It is important to determine if withholding feeds around transfusion reduces the risk of subsequent NEC and associated mortality. OBJECTIVES: • To assess the benefits and risks of stopping compared to continuing feed management before, during, and after blood transfusion in preterm infants • To assess the effects of stopping versus continuing feeds in the following subgroups of infants: infants of different gestations; infants with symptomatic and asymptomatic anaemia; infants who received different feeding schedules, types of feed, and methods of feed delivery; infants who were transfused with different blood products, at different blood volumes, via different routes of delivery; and those who received blood transfusion with and without co-interventions such as use of diuretics • To determine the effectiveness and safety of stopping feeds around the time of a blood transfusion in reducing the risk of subsequent necrotising enterocolitis (NEC) in preterm infants SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 11), in the Cochrane Library; MEDLINE (1966 to 14 November 2018); Embase (1980 to 14 November 2018); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 14 November 2018). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials (RCTs), cluster-RCTs, and quasi-RCTs. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials that compared stopping feeds versus continuing feeds around the time of blood transfusion in preterm infants. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed trial quality, and extracted data from the included studies. MAIN RESULTS: The search revealed seven studies that assessed effects of stopping feeds during blood transfusion. However, only one RCT involving 22 preterm infants was eligible for inclusion in the review. This RCT had low risk of selection bias but high risk of performance bias, as care personnel were not blinded to the study allocation. The primary objective of this trial was to investigate changes in mesenteric blood flow, and no cases of NEC were reported in any of the infants included in the trial. We were unable to draw any conclusions from this single study. The overall GRADE rating for quality of evidence was very low. AUTHORS' CONCLUSIONS: Randomised controlled trial evidence is insufficient to show whether stopping feeds has an effect on the incidence of subsequent NEC or death. Large, adequately powered RCTs are needed to address this issue.

PEBBLES study protocol: a randomised controlled trial to prevent atopic dermatitis, food allergy and sensitisation in infants with a family history of allergic disease using a skin barrier improvement strategy.

INTRODUCTION: The skin is an important barrier against environmental allergens, but infants have relatively impaired skin barrier function. There is evidence that impaired skin barrier function increases the risk of allergic sensitisation, atopic dermatitis (AD) and food allergy. We hypothesise that regular prophylactic use of emollients, particularly those that are designed to improve skin barrier structure and function, will help prevent these conditions. With the aim of determining if application of a ceramide-dominant emollient two times per day reduces the risk of AD and food allergy, we have commenced a multicentre phase III, outcome assessor blinded, randomised controlled trial of this emollient applied from birth to 6 months. METHODS AND ANALYSIS: Infants (n=760) with a family history of allergic disease will be recruited from maternity hospitals in Melbourne. The primary outcomes are as follows: the presence of AD, assessed using the UK Working Party criteria, and food allergy using food challenge, in the first 12 months of life as assessed by a blinded study outcome assessor. Secondary outcomes are as follows: food sensitisation (skin prick test), skin barrier function, AD severity, the presence of new onset AD after treatment cessation (between 6 and 12 months) and the presence of parent reported AD/eczema. Recruitment commenced in March 2018. ETHICS AND DISSEMINATION: The PEBBLES Study is approved by the Human Research Ethics Committees of the Royal Children's Hospital (RCH) (#37090A) and the Mercy Hospital for Women (2018-008). Parents or guardians will provide written informed consent. Outcomes will be disseminated through peer-reviewed publications and presented at scientific conferences. TRIAL REGISTRATION NUMBERS: ACTRN12617001380381 and NCT03667651.

Impact of intrauterine growth restriction on preterm lung disease.

AIM: Intrauterine growth restriction (IUGR) is an important cause for prematurity and adversely influences prematurity-related morbidities. This study evaluates the impact of IUGR on respiratory outcomes in infants <32 weeks with IUGR and birthweight <10th centile (SGA) compared to matched appropriate for gestation (AGA) controls. METHODS: The primary outcomes of this retrospective study are short-term pulmonary outcomes of chronic lung disease (CLD), CLD or death, and need for home oxygen at discharge. Subgroup analysis by gestation-based stratification (<28 and ≥28 <32 weeks) was decided a priori. RESULTS: Total of 153 IUGR and 306 non-IUGR infants were enrolled. The rate of CLD (45% vs. 17%, p = 0.0001), death (16% vs. 4.6%, p = 0.0001), CLD or death (46% vs. 21.5%, p = 0.0001), home oxygen rates (13.7% vs. 6.5%, p = 0.01) and duration of respiratory support was significantly higher in the IUGR group. IUGR emerged as the strongest predictor of CLD (adjusted OR, 95%CI: (8.4 [2, 35]) and CLD or death (12.7 [3, 54]) across all gestation. CONCLUSION: IUGR is a major risk factor for adverse short-term pulmonary outcomes as reflected by higher rates of CLD, CLD or death, and oxygen dependency at discharge in preterm infants.

Does fetal growth restriction lead to increased brain injury as detected by neonatal cranial ultrasound in premature infants?

AIM: Intra-uterine growth restriction (IUGR) is an important cause for prematurity as well as a significant risk factor for neurodevelopmental deficits. In this study, we aimed to examine the association between IUGR and early brain injury on neonatal cranial ultrasound in preterm infants. METHODS: This retrospective cohort study examined the relationship between IUGR and neonatal cranial ultrasound findings in preterm infants <32 weeks gestation with IUGR, compared with gestation and year of birth-matched appropriately grown infants, in a tertiary level neonatal unit. Primary outcome was incidence and severity of intraventricular haemorrhage (IVH), periventricular leucomalacia (PVL) and hydrocephalus detected by cranial ultrasound in the neonatal period. RESULTS: A total of 153 IUGR and 306 non-IUGR preterm infants <32 weeks were included. The rates of IVH (21.6% vs. 23.9%), severe IVH (3.9% vs. 4.6%), PVL (8.4% vs. 9.4%), cystic PVL (2.6% vs. 0%) and hydrocephalus (0.7% vs. 0.3%) were similar in the two groups. Composite outcome of death and severe brain injury (severe IVH, cystic PVL and hydrocephalus) was greater (20.2% vs. 9.1%, P = 0.001) in IUGR infants. CONCLUSION: IUGR did not lead to increased neonatal brain injury on cranial ultrasound but was associated with increased mortality. Advanced neonatal neuroimaging techniques may be necessary to estimate risk and to provide prognostic information of adverse neurological outcomes in this vulnerable population.

High flow nasal cannula for continuous positive airway pressure weaning in preterm neonates: A single-centre experience.

AIM: High flow nasal cannula therapy (HFNC) is an emerging method of non-invasive respiratory support therapy for premature infants. Recent evidence around its safety and efficacy for post-extubation respiratory support is encouraging. However, its effect on long-term respiratory outcomes is not known. The aim of this study is to determine the effect of HFNC on respiratory outcomes (chronic lung disease (CLD), need for home oxygen) when used to wean babies from continuous positive airway pressure (CPAP). METHODS: This retrospective study compared respiratory outcomes in infants born <32 weeks gestation needing any respiratory support at birth in two epochs - epoch I (2004-2007) verus epoch II (2008-2011). HFNC was available to be used as a CPAP weaning modality in epoch II. RESULTS: A total of 1286 infants (epoch I: 597 vs. epoch II: 689), mean (standard deviation) gestation, 28.1 (2.2) versus 28.5 (2.3) weeks were enrolled, with 222 (32%) receiving HFNC in epoch II. Overall median duration of respiratory support increased by 150 h in epoch II (P = 0.03), primarily as HFNC hours. A reduction in duration of invasive ventilation and CPAP along with 6% (P = 0.01) reduction in CLD rates was observed in epoch II. No change in home oxygen therapy rates was noted. In logistic regression, HFNC had no significant effect on rates of CLD or home oxygen. CONCLUSIONS: Introduction of HFNC for weaning nasal CPAP seems to have a minimal effect on CLD rates. The effect of HFNC on long-term outcomes needs to be further evaluated.

The Efficacy of Surfactant Replacement Therapy in the Growth-Restricted Preterm Infant: What is the Evidence?

BACKGROUND: Surfactant replacement therapy (SRT) is an integral part of management of preterm surfactant deficiency respiratory distress syndrome (RDS). Its role in the management of RDS has been extensively studied. However, its efficacy in the management of lung disease in preterm infants born with intrauterine growth restriction (IUGR) has not been systematically studied. OBJECTIVE: To evaluate the efficacy of exogenous SRT in the management of preterm IUGR lung disease. METHODS: A systematic search of all available randomized clinical trials (RCT) of SRT in preterm IUGR infants was done according to the standard Cochrane collaboration search strategy. Neonatal respiratory outcomes were compared between the preterm IUGR and appropriately grown for gestational age (AGA) preterm infant populations in eligible studies. RESULTS: No study was identified which evaluated the efficacy or responsiveness of exogenous SRT in preterm IUGR infants as compared to preterm AGA-infants. The only study identified through the search strategy used small for gestational age (SGA; defined as less than tenth centile for birth weight) as a proxy for IUGR. The RCT evaluated the efficacy or responsiveness of SRT in preterm SGA group as compared to AGA-infants. The rate of intubation, severity of RDS, rate of surfactant administration, pulmonary air leaks, and days on the ventilator did not differ between both groups. However, the requirement for prolonged nasal continuous positive airway pressure (p < 0.001), supplemental oxygen therapy (p < 0.01), and the incidence of bronchopulmonary dysplasia at 28 days and 36 weeks (both p < 0.01) was greater in SGA-infants. DISCUSSION: There is currently insufficient data available to evaluate the efficacy of SRT in preterm IUGR lung disease. A variety of research strategies will be needed to enhance our understanding of the role and rationale for use of SRT in preterm IUGR lung disease.

Use of inhaled nitric oxide in preterm infants: a regional survey of practices.

OBJECTIVES: To conduct a regional survey of neonatal intensive care unit (NICU) Directors in Australia and New Zealand (ANZ) to ascertain current practice. BACKGROUND: Use of inhaled nitric oxide (iNO) therapy in infants < 34 weeks gestational age is not supported by current evidence. METHODS: A cross-sectional electronic survey based on structured questionnaire was conducted amongst the Directors of all the tertiary neonatal intensive care units in Australia and New Zealand Neonatal Network (ANZNN). Information was collected on indications, dosage, monitoring response and weaning for iNO therapy. RESULTS: The survey was sent to 28 units, of which 2 were quaternary units' not routinely admitting preterm infants, hence were excluded from analysis. The response rate was 77% (20/26). Majority of units (16; 80%) did not have preterm specific protocol. In almost all units nitric was used as early rescue for hypoxemic respiratory failure (95%; 19/20). Neonatologist performed functional echocardiography (fECHO) was frequently used for prior assessment (90%) and monitoring (65%). Variations were noted regarding initiating criteria, dosage and weaning strategies. CONCLUSIONS: Wide variation in practice was noted highlighting the need for the formulation of consensus guidelines.

Congenital chylothorax: associations and neonatal outcomes.

AIM: Congenital chylothorax is a rare but significant neonatal entity with major morbidity and mortality. The study aims to describe the related associations, management and outcomes of this condition in neonates. METHODS: This is a retrospective case series of all cases of congenital chylothorax admitted to a tertiary neonatal centre in the last 15 years. RESULTS: Ten cases of congenital chylothorax were identified. Eight infants were diagnosed antenatally and three infants had antenatal pleural drainage. Most infants were ventilated at birth and required immediate pleurocentesis. Post-natal management included drainage of fluid, ventilation, albumin replacement, octreotide and dietary modification with medium-chain triglyceride-enriched formula. Five infants had chromosomal aberrations identified, while a further two had dysmorphic features not substantiated with routine genetic testing. Noonan's syndrome was the single most common underlying genetic diagnosis. Associated anomalies and malformations were present in 80% of the cohort. There were two deaths in the series, both in infants with multiple co-morbidities. CONCLUSIONS: Congenital chylothorax is a rare condition with overall prevalence of less than a case per year in our experience. Majority of infants had associated chromosomal anomalies and significant co-morbidities needing prolonged intensive care.

Vasopressin as an adjunct therapy for pulmonary hypertension: a case report.

UNLABELLED: Vasopressin is emerging as a therapeutic adjunct option towards treatment of shock states in the pediatric population. Its effects on pulmonary vasculature are less well understood. This report describes a 5-month-old infant with nitric oxide-unresponsive pulmonary hypertension, oxygenation failure, and systemic hypotension. Vasopressin therapy improved oxygenation and blood pressure and biventricular function, allowing weaning of nitric oxide and inotropic support. No decrease in coronary flow was noted. CONCLUSIONS: Vasopressin could be considered as an adjunct option in infants with pulmonary hypertension and systemic hypotension. Echocardiographic monitoring during treatment is recommended.

Neonatal meningitis and sepsis by Chryseobacterium indologenes: a rare and resistant bacterium.

Early neonatal meningitis with non-fermenting Gram negative bacilli (NFGNB) is rare, and whenever it occurrs, inanimate environment is usually implicated as the source. The authors report a case of neonatal meningitis and sepsis with Chryseobacterium indologenes, a rare non fermenting Gram negative bacterium with unusual antimicrobial susceptibility. Despite resistance to all the beta lactams, carbapenems and aminoglycosides, therapy with ciprofloxacin led to a favorable outcome.

Neonatal self-inflating bags: achieving titrated oxygen delivery using low flows: an experimental study.

AIM: To determine delivered O2 concentration (dFiO2) during manual inflations using neonatal self-inflating resuscitation bags (SIBs) at oxygen (O2) flow rates <1 L/min. METHODS: This experimental study, determined dFiO2 during 216 sets of manual inflations at different O2 flow rate (L/min; 0.2, 0.4, 0.6, 0.8, 1.0 and 5.0), controlling peak inspiratory pressures (PIP; cm of H2O; 10-15, 15-20 and 20-25), inflation rates (per min; 30, 40 and 60), with and without O2 reservoir using two SIBs--the Laerdal infant resuscitator (240 mL) and Ambu Mark IV resuscitator (300 mL). A leak proof circuit connecting the SIB in series with pressure transducer, O2 analyzer and test lung was used. All possible combinations were tested four times each. The dFiO2 with each possible combination was compared using generalised estimating equation. RESULTS: The mean dFiO2 with SIB even without reservoirs varied with rates and PIP from 75 to 93% at O2 flow rate of 5 L/min. At 1 L/min flow itself, 65-85% O2 is delivered. The dFiO2 was reduced to approximately 40% with flow of 0.2 L/min, PIP 20-25 cmH2O and inflations 40-60 per min. CONCLUSION: During manual breaths using neonatal SIBs, the delivered O2 concentration of nearly 40% is attained at clinically used inflation pressures and rates by using lower flows. A graded increase in O2 delivery from 40 to 99% was obtained with flow varying from 0.2 to 5 L/min and addition of reservoir. However, even at such low flows, reduction in O2 concentration below 40% was unattained.

Online Neonatal Training and Orientation Programme in India (ONTOP-IN)--the way forward for distance education in developing countries.

BACKGROUND: Internet-based distance learning combined with local hands-on skill enhancement can provide high-quality standardized education to in-service healthcare professionals in a wide geographical area. OBJECTIVE: Primary objective of this study was to evaluate the efficacy of internet-based distance learning in conjunction with local hands-on skill enhancement in improving knowledge and skills of essential newborn care among in-service nursing health professionals. METHODS: A total of 98 participants from seven health facilities in India and Maldives were enrolled in the study. Delivery of course material staggered over 5 weeks in the form of two lessons every week was moderated by two to three online tutors at each site. Participants managed actual case scenarios, participated in discussion forums and synchronous chat sessions within a closed group. Skill learning was administered by local tutor at the partnering health facilities. Knowledge and skill enhancement were evaluated by administering online multiple-choice questions (MCQs) test and on-site objective structured clinical evaluation (OSCE) stations before and after completion of the course. Participants' satisfaction was evaluated on a five-point Likert scale. RESULTS: Among 98 participants enrolled in the study, 78 (79%) completed the post-test assessment. There was significant increase in knowledge and skills scores (MCQ test: mean difference: 6.4 (95% CI: 5.6-7.17), OSCE: mean difference: 15.4 (95% CI: 12.7-18.1). All the participants expressed satisfaction with content and delivery of the learning module. CONCLUSION: To conclude, online training and teaching in essential newborn care is feasible and acceptable for in-service nursing professionals and serves as a useful tool for professional development of their practical skills and knowledge.

Patent ductus arteriosus in preterm infants.

Patent ductus arteriosus (PDA) is a major morbidity in preterm infants, especially in extremely premature infants less than 28 weeks. The clinical signs and symptoms of PDA in preterm infants are non specific and insensitive for making an early diagnosis of significant ductal shunting. Functional echocardiography is emerging as a new valuable bedside tool for early diagnosis of hemodynamically significant ductus, even though there are no universally accepted criteria for grading the hemodynamic significance. Echocardiography has also been used for early targeted treatment of ductus arteriosus, though the long term benefits of such strategy are debatable. The biomarkers like BNP and N terminal pro BNP are currently under research as diagnostic marker of PDA. The primary mode of treatment for PDA is pharmacological closure using cyclo-oxygenase inhibitors with closure rate of 70-80%. Oral ibuprofen is emerging as a better alternative especially in Indian scenario where parenteral preparations of indomethacin are unavailable and side effects are comparatively lesser. Though pharmacological closure of PDA is an established treatment modality, there is still lack of evidence for long term benefits of such therapy as well as there is some evidence for the possible adverse effects like increased ROP and BPD rates, especially if treated prophylactically. Hence, it is prudent to reserve treatment of PDA to infants with clinically significant ductus on the basis of gestation, birth weight, serial echocardiography and clinical status to individualize the decision to treat.

Potter syndrome with an unusual cardiac anomaly.

Potter syndrome is a congenital anomaly characterised by bilateral renal agenesis, pulmonary hypoplasia, cardiac, skeletal abnormalities and maternal oligohydramnios. Here we report a case of Potter syndrome with bilateral renal agenesis, pulmonary hypoplasia and complete transposition of the great vessels, which had been identified during a post-mortem examination. Although cardiac anomalies are known to exist with Potter syndrome, complete transposition of the great vessels has not been reported in the literature.