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An early manuscript note for Madame Bovary says that as a child, Emma believed in ‘l’homme qui jette du sable’. This article reveals that horrifying memories of ETA Hoffmann’s Sandman tale, which Flaubert read when very young, permeate Madame Bovary and continue to resurface throughout his work. The Sandman’s references to automata, dismemberment, burning or bleeding eyes, laboratories, furnaces, optical lenses, sand-throwing etc. resurface repeatedly in Madame Bovary or its drafts. Just as Hoffmann’s characters overlap or double as identities dissolve, so displaced elements of his tale circulate between Flaubert’s characters, adding deeply sinister undercurrents to the novel. Hoffmann’s reflexions on the process of literary creation have also left their mark. The obsessive presence of The Sandman seems related to traumatic events in Flaubert’s childhood. Once these intrusive memories are recognised in Flaubert’s writing, new light is shed on his fiction and on the relationship between traumatic memory and literary practice.

Prior to the introduction of newborn screening, Phenylketonuria (PKU) was a devastating disorder with affected individuals usually committed to a life in care in large institutions (asylums). Newborn screening only began after it was shown that those with PKU could be treated with a modified diet and could subsequently lead normal lives. The first production of a diet and the demonstration of its effectiveness was thus a key milestone in the history of both PKU and newborn screening, and took place in Birmingham, UK, in 1951. The pioneers were a two-year-old girl called Sheila Jones, her mother Mary, and three dedicated professionals at Birmingham Children’s Hospital: Evelyn Hickmans, John Gerrard and Horst Bickel. Together, they changed the course of PKU for those across the world. This review summarises the history and achievements of this team who opened the door to PKU treatment and the introduction of newborn screening.

Margaret H'Doubler brought the magic of dance to the 20th century, yet the 21st century has yet to find a person to rekindle the same public desire for dance education. Consequently, the future of dance education in the next century is hard to predict. Based on an informal survey of fellow advisory board members of Dance and the Child International, the author briefly profiles the status of dance education in a wide variety of countries and compares their status to the situation in the United States. Common barriers exist in answering the questions, "Who should teach, what should they teach, and who should teach the teachers?" The author recommends a clear course of action for advancing the cause of dance education, and suggests that dance educators have the ability to change government policies on the arts if they advocate with a strong united voice.

Abstract Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection in young children and the second leading cause of infant death worldwide. While global circulation has been extensively studied for respiratory viruses such as seasonal influenza, and more recently also in great detail for SARS-CoV-2, a lack of global multi-annual sampling of complete RSV genomes limits our understanding of RSV molecular epidemiology. Here, we capitalise on the genomic surveillance by the INFORM-RSV study and apply phylodynamic approaches to uncover how selection and neutral epidemiological processes shape RSV diversity. Using complete viral genome sequences, we show similar patterns of site-specific diversifying selection among RSVA and RSVB and recover the imprint of non-neutral epidemic processes on their genealogies. Using a phylogeographic approach, we provide evidence for air travel governing the global patterns of RSVA and RSVB spread, which results in a considerable degree of phylogenetic mixing across countries. Our findings highlight the potential of systematic global RSV genomic surveillance for transforming our understanding of global RSV spread.

Objectives . The role of race in late preterm respiratory morbidity has not been adequately described. We aimed to determine whether neonatal respiratory morbidity differs between Black and White late preterm infants. Methods . Single-centre retrospective cohort study at King’s College Hospital NHS Foundation Trust, London, UK of infants born at 34 to

Abstract Background Neurally adjusted ventilatory assist (NAVA) is a mode of mechanical ventilation that delivers oxygen pressures in proportion to electrical signals of the diaphragm. The proportional assistance can be adjusted by the clinician to reduce the patient’s work of breathing. Several case series of infants with congenital diaphragmatic hernias (CDH) have shown that NAVA may reduce oxygenation index and mean airway pressures. To date, no clinical trial has compared NAVA to standard methods of mechanical ventilation for babies with CDH. Methods The aim of this dual-centre randomised cross-over trial is to compare post-operative NAVA with assist control ventilation (ACV) for infants with CDH. If eligible, infants will be enrolled for a ventilatory support tolerance trial (VSTT) to assess their suitability for randomisation. If clinically stable during the VSTT, infants will be randomised to receive either NAVA or ACV first in a 1:1 ratio for a 4-h period. The oxygenation index, respiratory severity score and cumulative sedative medication use will be measured. Discussion Retrospective studies comparing NAVA to ACV in neonates with congenital diaphragmatic hernia have shown the ventilatory mode may improve respiratory parameters and benefit neonates. To our knowledge, this is the first prospective cross-over trial comparing NAVA to ACV. Trial registration NAN-C was prospectively registered on ClinicalTrials.gov NCT05839340 Registered on May 2023

The results of a survey of twenty-four neonatal units in the United Kingdom and Ireland are presented. A structured ten-item questionnaire was used, and demonstrated the variation in how infants with RS are diagnosed and managed. Notably, the survey revealed that a minority of infants were diagnosed antenatally. There were significant discrepancies in diagnostic criteria used and 79% of the units referred the patients to tertiary services. A preference for minimally invasive approaches to managing upper airway obstruction, such as a trial of prone positioning before progressing to a nasopharyngeal airway, was reported by 96% of the centers. A narrative review was undertaken which discusses the current practices for diagnosis and early management of Robin sequence (RS). The challenges of antenatal diagnosis, strategies to enhance outcomes through early detection and controversies surrounding the management of neonatal upper airway obstruction associated with RS are included. The results of the survey and our comprehensive review of the literature emphasize that there remains uncertainty regarding the best approach to treating Robin sequence.

End-tidal capnography can provide useful clinical information displayed on the ventilator screen or bedside monitor. It is important that clinicians can assess and utilise this information to assist in identifying underlying complications and pulmonary pathology. Sudden change or loss of the CO2 waveform can act as a safety measure in alerting clinicians of a dislodged or blocked endotracheal tube, considering the concurrent flow and volume waveforms. Visual pattern recognition by the clinicians of commonly seen waveform traces may act as an adjunct to other modes of ventilatory monitoring techniques. Waveforms traces can aid clinical management, help identify cases of ventilation asynchrony between the infant and the ventilator. We present some common clinical scenarios where tidal capnography can be useful in the timely identification of pulmonary complication and for practical troubleshooting at the cot-side.

Abstract Background Ventilated infants frequently require supplemental oxygen, but its use should be monitored carefully due to associated complications. The achievement of oxygen saturation (SpO2) targets can be challenging as neonates experience frequent fluctuations of their oxygen levels that further increase the risk of complications. Closed-loop automated oxygen control systems (CLAC) improve achievement of oxygen saturation targets, reduce hyperoxaemic episodes and facilitate weaning of the inspired oxygen concentration in ventilated infants born at or near term. This study investigates whether CLAC compared with manual oxygen control reduces the time spent in hyperoxia and the overall duration of supplemental oxygen treatment in ventilated infants born at or above 34 weeks gestation. Methods This randomised controlled trial performed at a single tertiary neonatal unit is recruiting 40 infants born at or above 34 weeks of gestation and within 24 h of initiation of mechanical ventilation. Infants are randomised to CLAC or manual oxygen control from recruitment till successful extubation. The primary outcome is the percentage of time spent in hyperoxia (SpO2 > 96%). The secondary outcomes are the overall duration of supplementary oxygen treatment, the percentage of time spent with an oxygen requirement above thirty per cent, the number of days on mechanical ventilation and the length of neonatal unit stay. The study is performed following informed parental consent and was approved by the West Midlands-Edgbaston Research Ethics Committee (Protocol version 1.2, 10/11/2022). Discussion This trial will investigate the effect of CLAC on the overall duration of oxygen therapy and the time spent in hyperoxia. These are important clinical outcomes as hyperoxic injury is related to oxidative stress that can adversely affect multiple organ systems. Trial registration ClinicalTrials.Gov NCT05657795. Registered on 12/12/2022.

(1) Background: Preterm premature rupture of membranes (PPROM) has been associated with increased perinatal morbidity, but the effect of PPROM on respiratory disease has not been previously quantified. We hypothesised that PPROM would be associated with a higher incidence of invasive ventilation. (2) Methods: A retrospective cohort study at the Neonatal Unit at King’s College Hospital NHS Foundation Trust, London, UK, was conducted on infants born before 37 weeks of gestation. PPROM was defined as the rupture of membranes for >48 h. (3) Results: We reviewed 1901 infants (434 with PPROM) with a median (IQR) gestational age of 32.4 (28.7–35.0) weeks. The median (IQR) duration of rupture of membranes in the infants with PPROM was 129 (78–293) h. The incidence of invasive ventilation was 56% in the infants with PPROM and 46% in the infants without PPROM (p < 0.001). Following regression analysis, PPROM was significantly related to a higher incidence of invasive ventilation (odds ratio: 1.48; 95% CI: 1.13–1.92, adjusted p = 0.004) after adjusting for birth weight [odds ratio = 0.34; 95% CI: 0.33–0.43, adjusted p < 0.001], Apgar score at 10 min [odds ratio =0.61; 95% CI: 0.56–0.66, adjusted p < 0.001] and antenatal corticosteroid use (adjusted p = 0.939). (4) Conclusions: PPROM was associated with a 1.48-fold higher risk of needing invasive ventilation.

Mechanical ventilation (MV), although life-saving, is associated with chronic respiratory morbidity in both preterm and term born infants. New ventilation modes have been developed with the aim of minimising lung injury. These include invasive and non-invasive respiratory support strategies, techniques for less invasive surfactant administration (LISA) and closed-loop automated oxygen control (CLAC) systems. Increasingly, newborn infants with signs of respiratory distress are stabilised on continuous positive airway pressure (CPAP) and receive LISA. Early CPAP when compared to mechanical ventilation reduced the incidence of BPD and respiratory morbidity at 18 to 22 months corrected age. Nasal intermittent positive pressure ventilation reduced treatment failure rates compared to CPAP, but not bronchopulmonary dysplasia (BPD). LISA compared with intubation and surfactant delivery reduced BPD, but there is no evidence from randomised trials regarding long-term respiratory and neurodevelopmental outcomes. Synchronisation of positive pressure inflations with the infant's respiratory efforts used with volume targeting should be applied for infants requiring intubation as this strategy reduces BPD. A large RCT with long term follow up data demonstrated that prophylactic high frequency oscillatory ventilation (HFOV) improved respiratory and functional outcomes at school age, but those effects were not maintained after puberty. CLAC systems appear promising, but their effect on long term clinical outcomes has not yet been explored in randomised trials. Further studies are required to determine the role of newer ventilation modes such as neurally adjusted ventilator assist (NAVA). All such respiratory support strategies should be tested in randomised controlled trials powered to assess long-term outcomes.

Abstract Background Many preterm infants require supplemental oxygen in the newborn period but experience frequent fluctuations of their oxygen saturation levels. Intermittent episodes of hypoxia or hyperoxia increase the risk of complications. Compliance with achievement of oxygen saturation targets is variable, and the need for frequent adjustments of the inspired oxygen concentration increases workload. Closed-loop automated oxygen control systems (CLAC) improve achievement of oxygen saturation targets and reduce both episodes of hypoxia and hyperoxia and the number of manual adjustments. This study investigates whether CLAC compared with manual oxygen control reduces the duration of mechanical ventilation in preterm infants born at less than 31 weeks of gestation. Methods This randomised controlled trial performed at a single tertiary neonatal unit is recruiting 70 infants born at less than 31 weeks of gestational age and within 48 h of initiation of mechanical ventilation. Infants are randomised to CLAC or manual oxygen control from recruitment until successful extubation. The primary outcome is the duration of mechanical ventilation, and secondary outcomes are the percentage of time spent within target oxygen saturation ranges, the time spent in hypoxia or hyperoxia, the number of manual adjustments required, the number of days on oxygen, the incidence of bronchopulmonary dysplasia and the length and cost of neonatal unit stay. The study is performed following informed parental consent and was approved by the Yorkshire and the Humber-Sheffield Research Ethics Committee (protocol version 1.1, 13 July 2021). Discussion This trial will investigate the effect of CLAC on the duration of mechanical ventilation, which is an important clinical outcome as prolonged mechanical ventilation is associated with important adverse outcomes, such as bronchopulmonary dysplasia. Trial registration ClinicalTrials.Gov NCT05030337 . Registered on 17 August 2021

BackgroundPatent ductus arteriosus (PDA) and diaphragmatic dysfunction are frequently seen in newborn infants but their relationship remains unknown. We aimed to use point of care ultrasound to compare diaphragmatic kinetics in infants with a PDA compared to in those without a PDA.MethodsM-mode ultrasonography was used to measure the mean inspiratory velocity (VI) in newborn infants with and without a haemodynamically significant PDA admitted in the Neonatal Unit at King's College Hospital during a three month period.ResultsSeventeen diaphragmatic ultrasound studies were reviewed from 14 infants with a median (IQR) gestational age of 26.1 (25.8–30.6) weeks, birth weight of 780 (660–1385) gr at a postnatal age of 18 (14–34) days. Eight scans had evidence of a PDA. The median (IQR) VI was significantly lower in scans with a PDA [1.01 (0.78–1.86) cm/s] compared to the ones without a PDA [3.21 (2.80–3.59) cm/s, p

BackgroundInfants born extremely preterm often suffer from respiratory disease and are invasively ventilated. We aimed to test the hypothesis that gas exchange in ventilated extremely preterm infants occurs both at the level of the alveoli and via mixing of fresh deadspace gas in the airways.MethodsWe measured the normalised slopes of phase II and phase III of volumetric capnography and related them with non-invasive measurements of ventilation to perfusion ratio (VA/Q) and right-to-left shunt in ventilated extremely preterm infants studied at one week of life. Cardiac right-to-left shunt was excluded by concurrent echocardiography.ResultsWe studied 25 infants (15 male) with a median (range) gestational age of 26.0 (22.9–27.9) weeks and birth weight of 795 (515–1,165) grams. The median (IQR) VA/Q was 0.52 (0.46–0.56) and shunt was 8 (2–13) %. The median (IQR) normalised slope of phase II was 99.6 (82.7–116.1) mmHg and of phase III was 24.6 (16.9–35.0) mmHg. The VA/Q was significantly related to the normalised slope of phase III (ρ = −0.573, p = 0.016) but not to the slope of phase II (ρ = 0.045, p = 0.770). The right-to-left shunt was not independently associated with either the slope of phase II or the slope of phase III after adjusting for confounding parameters.ConclusionsAbnormal gas exchange in ventilated extremely preterm infants was associated with lung disease at the alveolar level. Abnormal gas exchange at the level of the airways was not associated with quantified indices of gas exchange impairment.

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ObjectiveTo report values of the chest radiographic thoracic area (CRTA) in ventilated, term-born infants without respiratory disease and to evaluate whether CRTA is related to demographic data at birth.MethodsRetrospective, observational cohort study in a tertiary neonatal unit at King's College Hospital NHS Foundation Trust, London, UK.Newborn infants born after 36 completed weeks of gestation, ventilated for poor perinatal adaptation or hypoxic ischaemic encephalopathy without respiratory disease and admitted in a recent eight-year period (2014–2022).The CRTA was assessed by free-hand tracing of the perimeter of the thoracic area as outlined by the diaphragm and the rib cage excluding the mediastinal structures and was calculated using the Sectra PACS software.ResultsOne hundred and twenty-one infants (75 male) were included with a median (IQR) gestation of 40 (38–41) weeks and birth weight of 3.41 (3.04–3.75) kg. The median (IQR) CRTA was 2,589 (2,167–2,943) mm2 and was significantly related to birth weight (r = 0.316, p = 0.003), gestation at birth (r = 0.193, p = 0.032) and birth weight z-score (r = 0.187, p = 0.038).ConclusionsWe report values of the chest radiographic thoracic area in ventilated term-born infants which could be used as reference for determining respiratory disease severity.

Worldwide, three-quarters of a million babies are born extremely preterm (

Objective To assess the association of short-term neonatal outcomes with cross-site working of multiple healthcare professional teams between a level 3 and a level 1 neonatal unit.Design Retrospective cohort study.Setting A level 1 neonatal unit in London.Patients All infants admitted to the neonatal unit, between 2010 and 2021.Interventions The clinical service was rearranged in 2014 with the introduction of cross-site working between the level 1 unit and a level 3 unit of neonatal doctors, nurses and allied healthcare professionals.Main outcome measures Admission of infants with a temperature less than 36°C, length of stay and time to first consultation by a senior team member.Results A total of 4418 infants were admitted during the study period. The percentage of infants delivered at a gestation below 32 weeks was higher in the pre-cross-site period (8.9%) compared with the cross site period (3.6%, p

There is an association between very low birth weight (VLBW) and cardiovascular morbidity and mortality in adulthood. Aerobic fitness, measured as the maximal oxygen consumption (VO2 max), is a good indicator of cardiopulmonary health and predictor of cardiovascular mortality. Our aim was to determine the effect of birth weight on aerobic exercise capacity and physical activity. We systematically identified studies reporting exercise capacity (VO2 max and VO2 peak) and physical activity levels in participants born at VLBW aged eighteen years or older compared to term-born controls from six databases (MEDLINE, OVID, EMBASE, CI NAHL, CENTRAL, and Google Scholar). Meta-analysis of eligible studies was conducted using a random effect model. We screened 6202 articles and identified 15 relevant studies, 10 of which were eligible for meta-analysis. VLBW participants had a lower VO2 max compared to their term counterparts (−3.35, 95% CI: −5.23 to −1.47, p = 0.0005), as did VLBW adults who had developed bronchopulmonary dysplasia (−6.08, 95% CI −11.26 to −0.90, p = 0.02). Five of nine studies reported significantly reduced self-reported physical activity levels. Our systematic review and meta-analysis demonstrated reduced maximal aerobic exercise capacity in adults born at VLBW compared to term-born controls.

Background: Patent Ductus Arteriosus (PDA) is a common condition, affecting nearly half of infants born before 28 weeks' of gestation, and it has been associated with poor growth. It is not known if different treatment modalities are associated with more profound growth impairment. Our aim was to compare differences in weight gain at 36 weeks' corrected gestational age (CGA) in premature infants that received medical, surgical or conservative management for PDA. Methods: We retrospectively reviewed notes of 208 infants born under 30 weeks' gestation with a diagnosis of PDA. Gestational age (GA) at birth, birth weight z-score, CGA and weight z-score at 36 weeks' CGA were collected. In our cohort, surgical closure was performed in infants who remained symptomatic after medical or conservative management. Results: Ninety-four infants had medical, 56 surgical and 58 conservative management. Surgically managed infants had a lower median (IQR) GA [24.4 (24.0–26.1) weeks'] than medically [25.4 (24.6–26.5) weeks'] or conservatively managed [26.4 (25.4–28.1) weeks', p

Surfactant administered in the delivery suite might prevent or reduce the severity of subsequent respiratory distress syndrome. This review describes the evidence for surfactant delivery methods with relationship to their relevance in the delivery suite. The techniques include delivery using a thin catheter with the first breath, by the intubation-surfactant extubation procedure, less invasive surfactant administration (LISA) technique, using a laryngeal mask airway (LMA), or by nebulisation. There have been few randomised trials that have evaluated outcomes using these techniques in the delivery suite, and these were early trials. Currently, practitioners favour use of nasal continuous positive airway pressure with early rescue surfactant. Whether prophylactic surfactant given by the LISA technique or other techniques, such as via a LMA in the delivery suite, is more beneficial merits testing. This will require appropriately designed randomised trials with long-term outcomes.

Abstract Background Respiratory syncytial virus (RSV) is a global cause of severe respiratory morbidity and mortality in infants. While preventive and therapeutic interventions are being developed, including antivirals, vaccines and monoclonal antibodies, little is known about the global molecular epidemiology of RSV. INFORM is a prospective, multicenter, global clinical study performed by ReSViNET to investigate the worldwide molecular diversity of RSV isolates collected from children less than 5 years of age. Methods The INFORM study is performed in 17 countries spanning all inhabited continents and will provide insight into the molecular epidemiology of circulating RSV strains worldwide. Sequencing of > 4000 RSV-positive respiratory samples is planned to detect temporal and geographical molecular patterns on a molecular level over five consecutive years. Additionally, RSV will be cultured from a subset of samples to study the functional implications of specific mutations in the viral genome including viral fitness and susceptibility to different monoclonal antibodies. Discussion The sequencing and functional results will be used to investigate susceptibility and resistance to novel RSV preventive or therapeutic interventions. Finally, a repository of globally collected RSV strains and a database of RSV sequences will be created.

Congenital diaphragmatic hernia (CDH) is a rare developmental defect of the lungs and diaphragm, with substantial morbidity and mortality. Although internationally established treatment guidelines have been developed, most recommendations are still expert opinions. Trials in patients with CDH, more in particular randomized controlled trials, are rare. Only three multicenter trials in patients with CDH have been completed, which focused on fetoscopic tracheal occlusion and ventilation mode. Another four are currently recruiting, two with a focus on perinatal transition and two on the treatment of pulmonary hypertension. Herein, we discuss major challenges and pitfalls when performing a clinical trial in infants with CDH. It is essential to select the correct intervention and dose, select the appropriate population of CDH patients, and also define a relevant endpoint that allows a realistic duration and sample size. New statistical approaches might increase the feasibility of randomized controlled trials in patients with CDH. One should also timely perform the trial when there is still equipoise. But above all, awareness of policymakers for the relevance of investigator-initiated trials is essential for future clinical research in this rare disease.

Optimisation of respiratory support of infants with congenital diaphragmatic hernia (CDH) is critical. Infants with CDH often have severe lung hypoplasia and abnormal development of their pulmonary vasculature, leading to ventilation perfusion mismatch. It is vital that lung protective ventilation strategies are employed during both initial stabilisation and post-surgical repair to avoid ventilator induced lung damage and oxygen toxicity to prevent further impairment to an already diminished gas-exchanging environment. There is a lack of robust evidence for the routine use of surfactant therapy during initial resuscitation of infants with CDH and thus administration cannot be recommended outside clinical trials. Additionally, inhaled nitric oxide has been shown to have no benefit in reducing the mortality rates of infants with CDH. Other therapeutic agents which beneficially act on pulmonary hypertension are currently being assessed in infants with CDH in randomised multicentre trials. The role of novel ventilatory modalities such as closed loop automated oxygen control, liquid ventilation and heliox therapy may offer promise for infants with CDH, but the benefits need to be determined in appropriately designed clinical trials.

Background During neurally adjusted ventilatory assist (NAVA)/noninvasive (NIV) NAVA, a modified nasogastric feeding tube with electrodes monitors the electrical activity of the diaphragm (Edi). The Edi waveform determines the delivered pressure from the ventilator. Objective Our objective was to determine whether NAVA/NIV-NAVA has advantages in infants with evolving/established bronchopulmonary dysplasia (BPD). Methods Each infant who received NAVA/NIV-NAVA and conventional invasive and NIV was matched with two historical controls. Eighteen NAVA/NIV-NAVA infants’ median gestational age, 25.3 (23.6–28.1) weeks, was compared with 36 historical controls’ median gestational age 25.2 (23.1–29.1) weeks. Results Infants on NAVA/NIV-NAVA had lower extubation failure rates (median: 0 [0–2] vs. 1 [0–6] p = 0.002), shorter durations of invasive ventilation (median: 30.5, [1–90] vs. 40.5 [11–199] days, p = 0.046), and total duration of invasive and NIV to the point of discharge to the local hospital (median: 80 [57–140] vs. 103.5 [60–246] days, p = 0.026). The overall length of stay (LOS) was lower in NAVA/NIVNAVA group (111.5 [78–183] vs. 140 [82–266] days, p = 0.019). There were no significant differences in BPD (17/18 [94%] vs. 32/36 [89%] p = 0.511) or home oxygen rates (14/18 [78%] vs. 23/36 [64%] p = 0.305). Conclusion The combination of NAVA/NIV-NAVA compared with conventional invasive and NIV modes may be advantageous for preterm infants with evolving/established BPD.

Hypopituitarism in neonates is rare, but has life-threatening complications if untreated. This review describes the features of hypopituitarism and the evidence for which infants in whom a genetic cause should be suspected. Importantly, neonates are often asymptomatic or present with non-specific symptoms. Hypopituitarism can be due to abnormal gland development as a result of genetic defects, which result from mutations in gene coding for transcription factors which regulate pituitary development. The mutations can be divided into those causing isolated hypopituitarism or those causing syndromes with associated hypopituitarism. The latter involve mutations in transcription factors which regulate pituitary, as well as extra-pituitary development. There is a paucity of evidence as to which patients should be investigated for genetic mutations, but detailed clinical and biochemical phenotyping with magnetic resonance imaging of the pituitary gland could help target those in whom genetic investigations would be most appropriate.

Abstract Background Follow-up studies of infants born prematurely are essential to understand the long-term consequences of preterm birth and the efficacy of interventions delivered in the neonatal period. Retention of participants for follow-up studies, however, is challenging, with attrition rates of up to 70%. Our aim was to examine retention rates in two follow-up studies of prematurely born children and identify participant or study characteristics that were associated with higher attrition, and to discuss retention strategies with regard to the literature. Methods Data from children recruited at birth to one of two studies of prematurely born infants were assessed. The two studies were the United Kingdom Oscillation Study (UKOS, a randomised study comparing two modes of neonatal ventilation in infants born less than 29 weeks of gestational age (GA)), and an observational study examining the impact of viral lower respiratory tract infections in infancy in those born less than 36 weeks of GA (virus study). The UKOS participants, but not those in the virus study, had regularly been contacted throughout the follow-up period. UKOS subjects were followed up at 11 to 14 years of age and subjects in the virus study at 5–7 years of age. At follow up in both studies, pulmonary function and respiratory morbidity were assessed. Retention rates to follow-up in the two studies and baseline characteristics of those who were and were not retained were assessed. Results Retention was significantly higher in UKOS than the virus study (61% versus 35%, p

Background Less invasive surfactant administration (LISA) is the preferred mode of surfactant administration for spontaneously breathing preterm babies supported by noninvasive ventilation (NIV). Objective The aim of this study was to determine whether LISA on the neonatal unit or in the delivery suite was associated with reduced rates of bronchopulmonary dysplasia (BPD) or the need for intubation, or lower durations of invasive ventilation and length of hospital stay (LOS). Methods A historical comparison was undertaken. Each “LISA” infant was matched with two infants (controls) who did not receive LISA. Results The 25 LISA infants had similar gestational ages and birth weights to the 50 controls (28 [25.6–31.7] weeks vs. 28.5 [25.4–31.9] weeks, p = 0.732; 1,120 (580–1,810) g vs. 1,070 [540–1,869] g, p = 0.928), respectively. LISA infants had lower requirement for intubation (52 vs. 90%, p

Zusammenfassung Im Jahr 1820 traten zwei Universitätsabsolventen, Christian Gottfried Ehrenberg und Wilhelm Hemprich, eine Forschungsreise nach Nordafrika an, die eine der ersten vom preußischen Staat maßgeblich getragenen Reiseunternehmungen darstellt. Wesentliches Ziel der Reise war das Sammeln von naturkundlichen Exemplaren für die junge Berliner Museumslandschaft. Der Beitrag ordnet die afrikanische Forschungsreise in die wissenschaftliche Laufbahn Ehrenbergs ein, der als einziger Reisender überlebte, sowie in die Geschichte der Berliner Wissenschaftslandschaft im frühen 19. Jahrhundert. Dabei konzentriert sich der Beitrag auf die Medien – insbesondere Sammlungsverzeichnisse und Sammlungsobjekte – die die Reisenden im Feld einsetzen mussten, um ihre Identität als gelehrte Naturforscher gegenüber ihren Förderern zu inszenieren und damit ihre Position in der preußischen Wissenschaft strategisch zu sichern. Abstract In 1820, two university graduates, Christian Gottfried Ehrenberg and Wilhelm Hemprich, embarked on a research expedition to North Africa, one of the first travel ventures funded by the Prussian state. The main goal of the trip was to collect natural history specimens for the Berlin museums. The article contextualizes the research voyage within the scientific career of Ehrenberg, the only surviving member of the voyage, and in the history of Berlin's scientific landscape in the early 19th century. The article focuses on the media – particularly collection inventories and collection objects – that the travelers implemented in the field to fashion their identity as learned naturalists and thus strategically secure their position in Prussian science. Résumé En 1820, deux diplômés de lʼuniversité, Christian Gottfried Ehrenberg et Wilhelm Hemprich, se sont lancés dans une expédition de recherche en Afrique du Nord, lʼune des premières expéditions de voyage à bénéficier dʼun soutien important de lʼÉtat prussien. Le but principal du voyage était de collecter des spécimens d'histoire naturelle pour le jeune paysage muséal de Berlin. Le présent article se propose de situer le voyage de recherche en Afrique dans la carrière scientifique dʼEhrenberg, le seul voyageur survivant, ainsi que dans lʼhistoire de lʼinfrastructure scientifique de Berlin au début du XIXe siècle. Dans ce but, lʼarticle se concentre sur les médias – en particulier les inventaires et les objets de collection – que les voyageurs ont dû utiliser sur le terrain pour mettre en scène leur identité de naturalistes cultivés vis-à-vis de leurs mécènes afin d’assurer stratégiquement leur position dans la science prussienne.

The forced oscillation technique (FOT) is a non-volitional assessment that is used during tidal breathing. A variant of FOT uses a pseudorandom noise (PRN) signal which we postulated might have utility in assessing lung function in prematurely born children. We, therefore, undertook a systematic review to evaluate the evidence regarding PRN FOT. A comprehensive search of the literature was conducted by using the following databases: Medline, Embase, Web of Science and CINAHL. Observational studies, case series/reports and randomized-controlled trials were eligible for inclusion. Article abstracts and full texts were screened independently by two reviewers, with disagreements resolved by discussion or a third reviewer if necessary. Five studies were included (n = 587 preterm children). Three compared PRN FOT with spirometry, and two compare it to the interrupter technique. Most studies failed to report comprehensive methodology of the frequency spectra used to generate the PRN signal. There was evidence that poorer lung function, as assessed by PRN FOT, was associated with a greater burden of respiratory symptoms, but there was insufficient evidence to determine whether PRN FOT performed better than other lung-function tests. Detailed methodological documentation, in accordance with ERS guidance, is needed to assess the benefits of PRN FOT prior to routine clinical incorporation to assess prematurely born children.

Maternal smoking is a risk factor for both sudden infant death syndrome (SIDS) and sudden intrauterine unexplained death syndrome (SIUDS). Both SIDS and SIUDS are more frequently observed in infants of smoking mothers. The global prevalence of smoking during pregnancy is 1.7% and up to 8.1% of women in Europe smoke during pregnancy and worldwide 250 million women smoke during pregnancy. Infants born to mothers who smoke have an abnormal response to hypoxia and hypercarbia and they also have reduced arousal responses. The harmful effects of tobacco smoke are mainly mediated by release of carbon monoxide and nicotine. Nicotine can enter the fetal circulation and affect multiple developing organs including the lungs, adrenal glands and the brain. Abnormalities in brainstem nuclei crucial to respiratory control, the cerebral cortex and the autonomic nervous system have been demonstrated. In addition, hypodevelopment of the intermediolateral nucleus in the spinal cord has been reported. It initiates episodic respiratory movements that facilitate lung development. Furthermore, abnormal maturation and transmitter levels in the carotid bodies have been described which would make infants more vulnerable to hypoxic challenges. Unfortunately, smoking cessation programs do not appear to have significantly reduced the number of pregnant women who smoke.

Abstract Background Research evaluating lifestyle interventions for prevention of cardiovascular disease (CVD) may not reach those most at risk. We compared the response rate to a randomised controlled trial (RCT) of a lifestyle intervention by CVD risk, ethnicity and level of deprivation. Methods Primary care patients with a QRisk2 score ≥ 20% were invited to participate in a RCT of an intensive lifestyle intervention versus usual care. This cross-sectional analysis compares anonymised data of responders and non-responders with multiple logistic regression, using adjusted odds ratios (AORs) for QRisk2 score, ethnicity, Index of Multiple Deprivation (IMD 2010) quintile, age and sex. Results From 60 general practices, 8902 patients were invited and 1489 responded. The mean age was 67.3 years and 21.0% were female. Of all patients invited, 69.9% were of white ethnic background, 13.9% ethnic minority backgrounds and 16.2% had no ethnicity data recorded in their medical records. Likelihood of response decreased as QRisk2 score increased (AOR 0.82 per 5 percentage points, 95% CI 0.77–0.88). Black African or Caribbean patients (AOR 0.67; 95% CI 0.45–0.98) and those with missing ethnicity data (AOR 0.55; 95% CI 0.46–0.66) were less likely to respond compared to participants of white ethnicity, but there was no difference in the response rates between south Asian and white ethnicity (AOR 1.08; 95% CI 0.84–1.38). Patients residing in the fourth (AOR 0.70; 95% CI 0.56–0.87) and fifth (AOR 0.52; 95% CI 0.40–0.68) most deprived IMD quintile were less likely to respond compared to the least deprived quintile. Conclusions Evaluations of interventions intended for those at high risk of CVD may fail to reach those at highest risk. Hard to reach patient groups may require different recruitment strategies to maximise participation in future trials. Improvements in primary care ethnicity data recording is required to aid understanding of how successfully study samples represent the target population. Trial registration ISRCTN, ISRCTN84864870. Registered 15 May 2012, https://doi.org/10.1186/ISRCTN84864870.

Background: We aimed to determine whether the introduction of 24 h cover by resident consultants in a tertiary neonatal unit affected mortality and other clinical outcomes. Methods: Retrospective cohort study in a tertiary medical and surgical neonatal unit between 2010–2020 of all liveborn infants admitted to the neonatal unit. Out of hours cover was rearranged in 2014 to ensure 24 h presence of a senior trained neonatologist (resident consultant). Results: In the study period, 4778 infants were included: 2613 in the pre-resident period and 2165 in the resident period. The median (IQR) time to first consultation by a senior member of staff was significantly longer in the pre-resident period [1.5 (0.6–4.3) h] compared to the resident period [0.5 (0.3–1.5) h, p < 0.001]. Overall, mortality was similar in the pre-resident and the resident periods (3.2% versus 2.3%, p = 0.077), but the mortality of infants born at night was significantly higher in the pre-resident (4.5%) compared to the resident period (2.5%, p = 0.016). The resident period was independently associated with an increased survival to discharge (adjusted p < 0.001, odds ratio: 2.0) after adjusting for gestational age, admission temperature and duration of ventilation. Conclusions: Following introduction of a resident consultant model the mortality and time to consultation after admission decreased.

Abstract Background Many infants born at less than 34 weeks of gestational age will require resuscitation in the delivery suite. Yet, different resuscitation techniques are specified in different national guidelines, likely reflecting a limited evidence base. One difference is the length of mechanical inflation initially delivered to infants either via a facemask or endotracheal tube. Some guidelines specify short inflations delivered at rates of 40–60/min, others recommend initial inflations lasting 2–3 s or sustained inflations lasting for ≥ 5 s for initial resuscitation. Research has shown that tidal volumes > 2.2 mL/kg (the anatomical dead space) are seldom generated unless the infant’s respiratory effort coincides with an inflation (active inflation). When inflations lasting 1–3 s were used, the time to the first active inflation was inversely proportional to the inflation time. This trial investigates whether a sustained inflation or repeated shorter inflations is more effective in stimulating the first active inflation. Methods This non-blinded, randomised controlled trial performed at a single tertiary neonatal unit is recruiting 40 infants born at

Howard Gardner's Theory of Multiple Intelligences (MI theory) can be integrated into dance classes to make them more effective. When dance educators include activities that strengthen the musical, visual, linguistic, logical-mathematical, interpersonal, intrapersonal, and bodily-kinesthetic intelligences into every class, each student is touched and learning increased. The integration of these activities leads to best practices in dance education, creating classes that go beyond simple dance technique. Brain research has provided insights into “brain compatible” teaching and how students learn. MI theory addresses these principles. Suggestions for integrating MI theory into teaching are presented. [ABSTRACT FROM PUBLISHER]

We previously demonstrated corticosteroid administration on the neonatal intensive care unit was associated with reduced lung function at 11 to 14 years of age in children born very prematurely. The objective of this observational study was to assess if lung function remained impaired at 16 to 19 years of age in those who had received postnatal corticosteroids and whether the trajectory of lung function with increasing age differed between those who had and had not received corticosteroids. One hundred and fifty-nine children born prior to 29 weeks of gestational age had comprehensive lung function measurements; 49 had received postnatal dexamethasone. Lung function outcomes were compared between those who had and had not received postnatal dexamethasone after adjustment for neonatal factors. Forced expiratory flow at 75%, 50%, 25% and 25-75% of the expired vital capacity, forced expiratory volume in one second, peak expiratory flow and forced vital capacity and lung volumes (total lung capacity and residual volume) were assessed. The majority of results were significantly lower in those who received dexamethasone (between 0.61 to 0.78 standard deviations). Lung function reduced as the number of courses of dexamethasone increased. Between 11 and 14 years and 16 to 19 years, lung function improved in the unexposed group, but forced expiratory flow at 75% of the expired vital capacity and forced expiratory volume in one second deteriorated in those who had received postnatal corticosteroids (p = 0.0006). These results suggest that prematurely born young people who received postnatal corticosteroids may be at risk of premature onset of chronic obstructive pulmonary disease.

Background. Bilious vomiting in the newborn is common and requires urgent attention to exclude malrotation. The proportion of neonates with surgical abnormalities, however, is small, and there are other causes. Study Objectives. We reviewed our experience of infants with bilious vomiting to demonstrate the importance of input from the tertiary surgical and medical team to arrive at the correct diagnosis. Design. Admissions with bilious vomiting/aspirates of term born infants over a three-year period to a tertiary medical and surgical unit were reviewed. Results. During the study period, 48 infants were admitted with bilious vomiting. Forty-five infants had upper gastrointestinal (UGI) contrast studies, and only six had an abnormal study: four had malrotation and two had Hirschsprung’s disease. Of the infants with a normal UGI study, no cause was identified in 20 cases, 13 infants were treated for sepsis, one had a meconium plug, one an ovarian cyst, and two infants were polycythaemic. One infant was diagnosed with bilateral polymicrogyria (PMG) on brain MRI and another was found to have hypochondroplasia FGFR3 skeletal dysplasia. Conclusion. Neonates with bilious vomiting may have a variety of underlying diagnoses and need to be referred to a tertiary surgical and medical centre to ensure appropriate diagnosis is made.

Background: Motivational interviewing (MI) enhanced with behaviour change techniques (BCTs) and deployed by health trainers targeting multiple risk factors for cardiovascular disease (CVD) may be more effective than interventions targeting a single risk factor. Objectives: The clinical effectiveness and cost-effectiveness of an enhanced lifestyle motivational interviewing intervention for patients at high risk of CVD in group settings versus individual settings and usual care (UC) in reducing weight and increasing physical activity (PA) were tested. Design: This was a three-arm, single-blind, parallel randomised controlled trial. Setting: A total of 135 general practices across all 12 South London Clinical Commissioning Groups were recruited. Participants: A total of 1742 participants aged 40–74 years with a ≥ 20.0% risk of a CVD event in the following 10 years were randomised. Interventions: The intervention was designed to integrate MI and cognitive–behavioural therapy (CBT), delivered by trained healthy lifestyle facilitators in 10 sessions over 1 year, in group or individual format. The control group received UC. Randomisation: Simple randomisation was used with computer-generated randomisation blocks. In each block, 10 participants were randomised to the group, individual or UC arm in a 4 : 3 : 3 ratio. Researchers were blind to the allocation. Main outcome measures: The primary outcomes are change in weight (kg) from baseline and change in PA (average number of steps per day over 1 week) from baseline at the 24-month follow-up, with an interim follow-up at 12 months. An economic evaluation estimates the relative cost-effectiveness of each intervention. Secondary outcomes include changes in low-density lipoprotein cholesterol and CVD risk score. Results: The mean age of participants was 69.75 years (standard deviation 4.11 years), 85.5% were male and 89.4% were white. At the 24-month follow-up, the group and individual intervention arms were not more effective than UC in increasing PA [mean 70.05 steps, 95% confidence interval (CI) –288 to 147.9 steps, and mean 7.24 steps, 95% CI –224.01 to 238.5 steps, respectively] or in reducing weight (mean –0.03 kg, 95% CI –0.49 to 0.44 kg, and mean –0.42 kg, 95% CI –0.93 to 0.09 kg, respectively). At the 12-month follow-up, the group and individual intervention arms were not more effective than UC in increasing PA (mean 131.1 steps, 95% CI –85.28 to 347.48 steps, and mean 210.22 steps, 95% CI –19.46 to 439.91 steps, respectively), but there were reductions in weight for the group and individual intervention arms compared with UC (mean –0.52 kg, 95% CI –0.90 to –0.13 kg, and mean –0.55 kg, 95% CI –0.95 to –0.14 kg, respectively). The group intervention arm was not more effective than the individual intervention arm in improving outcomes at either follow-up point. The group and individual interventions were not cost-effective. Conclusions: Enhanced MI, in group or individual formats, targeted at members of the general population with high CVD risk is not effective in reducing weight or increasing PA compared with UC. Future work should focus on ensuring objective evidence of high competency in BCTs, identifying those with modifiable factors for CVD risk and improving engagement of patients and primary care. Trial registration: Current Controlled Trials ISRCTN84864870. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 69. See the NIHR Journals Library website for further project information. This research was part-funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London.

Introduction Congenital diaphragmatic hernia (CDH) is a developmental defect of the diaphragm that impairs normal lung development, causing pulmonary hypertension (PH). PH in CDH newborns is the main determinant for morbidity and mortality. Different therapies are still mainly based on ‘trial and error’. Inhaled nitric oxide (iNO) is often the drug of first choice. However, iNO does not seem to improve mortality. Intravenous sildenafil has reduced mortality in newborns with PH without CDH, but prospective data in CDH patients are lacking.Methods and analysis In an open label, multicentre, international randomised controlled trial in Europe, Canada and Australia, 330 newborns with CDH and PH are recruited over a 4-year period (2018–2022). Patients are randomised for intravenous sildenafil or iNO. Sildenafil is given in a loading dose of 0.4 mg/kg in 3 hours; followed by continuous infusion of 1.6 mg/kg/day, iNO is dosed at 20 ppm. Primary outcome is absence of PH on day 14 without pulmonary vasodilator therapy and/or absence of death within the first 28 days of life. Secondary outcome measures include clinical and echocardiographic markers of PH in the first year of life. We hypothesise that sildenafil gives a 25% reduction in the primary outcome from 68% to 48% on day 14, for which a sample size of 330 patients is needed. An intention-to-treat analysis will be performed. A p-value (two-sided)

Objectives To ascertain parental views regarding taking part in neonatal unit ward rounds.Design A service evaluation project.Setting Tertiary neonatal intensive care unit.Patients Parent(s) of infants receiving care on the neonatal unit.Interventions Structured interviews conducted at the cot side.Main outcome measures Parents were asked if they knew when ward rounds occurred, whether they had attended ward rounds and if they had not what were the factors inhibiting them from doing so, their experience of attending ward rounds and whether they were concerned about issues of confidentiality.Results 23 of 24 consecutive parents agreed to be interviewed. The median age of their infants was 14 (range 3 – 123) days when they were interviewed. Eighty-five per cent were able to identify when a nursing handover or doctor’s ward round occurred. Seventy-five per cent of parents had attended at least one ward round and the median score in terms of usefulness was 5 out of 5. Reasons for not attending included time and cost to travel to the unit, their partners were working and having other children. Parents volunteered that the nurses proactively updated them as soon as they arrived, hence making regular attendance less important. Regarding confidentiality, 85% were not concerned if other people overheard information about their baby, unless the news was bad.Conclusions Parents recognised the value of attending ward rounds and generally found it a positive experience, but emphasised limitations on their ability to attend.

Background. Neonatal chylothorax is a rare condition, but has a high mortality. Study Objectives. To analyse the outcomes of a series of neonates with chylothorax and review the literature to determine best practice. Design. A case series review and a literature review using electronic databases including the key words neonates and chylothorax. Results. Six cases of neonatal chylothorax were identified during a ten-year period, two had congenital chylothoraces and four iatrogenic chylothoraces after thoracic surgery or chest instrumentation. The neonates were ventilated for a median of 30 (range 13–125) days with a median maximum daily pleural fluid output of 218 (range 86–310) ml/kg/day. All the neonates were given medium-chain triglyceride (MCT) feeds which stabilised pleural fluid output in four and reduced it in another. Octreotide was used in three neonates, but the dosage used had no significant effect on pleural output. Two neonates required surgical intervention. The literature review demonstrated MCT feeds can reduce or stabilise pleural fluid output, but highlighted variable use of octreotide and inconsistent dosing regimens and outcomes. No consensus regarding indications for surgical intervention was identified. Summary and Conclusion. Neonatal chylothorax is uncommon, but affected neonates require high healthcare utilisation.

Objectives To determine whether paediatricians are supported by their organisations to encourage patient and public involvement (PPI) in research activities and clinical improvement work, the challenges they face and how they think these could be addressed by the Royal College of Paediatrics and Child Health (RCPCH).Design A survey.Setting UK consultant paediatricians and staff associate specialist and specialty (SAS) doctors who are members of RCPCH.Main outcome measures The proportion of respondents who said that PPI was central to research and service improvements in their organisation, the type of local support for PPI activity, challenges in undertaking PPI and the support members wanted from RCPCH.Results There was a response rate of 44.4% (n=1924). In their organisation, 29.1% of respondents stated PPI was central to research and 36.1% to service improvement; 46% were unaware of support for PPI and 15% said there was no support. The main challenges for PPI activity were a lack of clinician time, local support and funding. Respondents wanted RCPCH to advocate for protected time for PPI, provide access to PPI groups and deliver guidance and training.Conclusions The majority of paediatricians feel unsupported to undertake PPI activity by their local organisation. The RCPCH has a key role to enable all paediatricians to work with children, young people and their carers to improve the quality of research and clinical services as demonstrated by RCPCH’s ongoing activity in these crucial and important areas.

Methemoglobinemia can result in severe hypoxia. It has been frequently reported during the use of inhaled nitric oxide, but can occur where nitrate containing medications are used. Glyceryl trinitrate (GTN) patches have been used in the treatment of digital and limb ischemia in prematurely born infants. Little is known about the pharmacokinetics of GTN when incorporated into patches. Studies of other topical forms of nitroglycerine have shown a wide range of absorption. It is likely that the increased permeability of the prematurely born infant's skin would facilitate absorption. We describe the use of GTN patches in two very prematurely born infants used to treat limb/digit ischemia. This resulted in methemoglobinemia and resultant increase in their supplementary oxygen requirements. Removal of the patches was associated with a reduction in their methemoglobin levels and the supplementary oxygen requirements back to baseline levels. In conclusion, routine monitoring of methemoglobin levels should be undertaken when GTN patches are used in very prematurely born infants.

Objective Multiple outcomes can be measured in infants that receive neonatal care. It is unknown whether outcomes of importance to parents and patients differ from those of health professionals. Our objective was to systematically map neonatal care outcomes discussed in qualitative research by patients, parents and healthcare professionals and test whether the frequency with which outcomes are discussed differs between groups.Design Systematic review of qualitative literature. The following databases were searched: Medline, CINAHL, EMBASE, PsycINFO and ASSIA from 1997 to 2017. Publications describing qualitative data relating to neonatal care outcomes, reported by former patients, parents or healthcare professionals, were included. Narrative text was analysed and outcomes grouped thematically by organ system. Permutation testing was applied to assess an association between the outcomes identified and stakeholder group.Results Sixty-two papers containing the views of over 4100 stakeholders were identified; 146 discrete outcomes were discussed; 58 outcomes related to organ systems and 88 to other more global domains. Permutation testing provides evidence that parents, former patients and health professionals reported outcomes with different frequencies (p=0.037).Conclusions Parents, patients and health professionals focus on different outcomes when discussing their experience of neonatal care. A wide range of neonatal care outcomes are reported in qualitative research; many are global outcomes relating to the overall status of the infant. The views of former patients and parents should be taken into consideration when designing research; the development of a core outcomes set for neonatal research will facilitate this.