41 e-Letters

published between 2018 and 2021

  • End-expiratory pressure during the respiratory transition: a more complex tale?

    Dear Editors,
    I read with interest the review article of Martherus and co-workers entitled ‘Supporting breathing of preterm infants at birth: a narrative review’. Despite the ongoing focus on the respiratory transition at birth, clinical strategies that improve outcome are lacking. As such the authors should be congratulated on this timely review. As they emphasise, there is still a dearth of human data, and much of the literature regarding pressure strategies at birth remains in the domain of preclinical studies. The authors thus appropriately focused on the preclinical literature with regards to CPAP and PEEP levels, acknowledging that end-expiratory pressure remains the foundation of respiratory support. Table 1 and the accompanying text unfortunately do not fully achieve the authors stated aims of providing a summary of ‘the currently available literature’ concerning the ‘effect of different CPAP strategies in the very preterm lung at birth.’ Whilst this section provides a nice summary of six worthy studies arising predominantly from the authors’ own lab it cannot be considered inclusive or complete.

    The authors suggest that PEEP titration maybe useful during the respiratory transition. In 2014 we were the first to report the use of a high PEEP titration strategy at birth in preterm lambs, providing an escalating and then de-escalating PEEP (dynamic) strategy with transient PEEP levels up to 20 cmH2O. We demonstrated improved oxygenation and lung mechanic...

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  • Anesthesia in delivery room and respiratory drive


    Dear Editor
    We were honoured to read the kind comment from Dr Subhash C Shaw (1) concerning our article « Nasal midazolam vs ketamine for neonatal intubation in the delivery room: a randomised trial” by Milési et al published in Arch Dis Child Fetal Neonatal Ed 2018; 103: F221-F226.1 » (2).
    Dr Shaw rose several important questions:
    He questions the possibility to keep a good respiratory drive with an anaesthetic procedure in delivery room. At the time of this study (2012) we were not using the INSURE procedure. For two years we are using the “Less Invasive Ventilation (LISA)” with a sedation protocol. Our protocol is proposing either intra-venous (IV) KETAMINE (0.5 mg/kg) or intra-nasal (IN) (0.2 mg/kg) MIDAZOLAM if an IV line is unavailable. Keeping a good respiratory drive is a key issue with this new technique. Therefore the anaesthetic issue is a very challenging one. Several authors show that it was possible to insure a good sedation level while keeping a good respiratory drive (3-5). In our experience with LISA and IN MIDAZOLAM (personal data) the success rate defined by the absence of intubation within the first 72 hours occurred in 7/10 of the cases, which was similar to the one described in the literature with or without any sedation (3-6).
    There are still some controversies regarding MIDAZOLAM safety. This drug is widely used in Europe (7). The myoclonic movements are...

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  • Response to letter re: ‘Combinations of subgroup analyses and impact on results’

    We thank the letter authors for commending most of our protocol decisions. A multicenter trial is always associated with a number of compromises, e.g.  between standardization and freedom of therapy, between insufficient and overzealous data collection, and between too few and too many exploratory statistical tests.


    For detecting BPD, we used criteria that included all cases with requirement of supplemental oxygen or mechanical support at a postmenstrual age of 36 weeks. This definition was the same as moderate or severe BPD in the more recently formulated consensus definition, and has been used in many other previous trials, testing ventilation modes, high-frequency ventilation, steroid use, permissive hypercapnia, and many others. This made our results comparable to previously published data.

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    Dear Editor,
    We read with great interest the article “Nasal midazolam vs ketamine for neonatal intubation in the delivery room: a randomised trial” by Milési et al published in Arch Dis Child Fetal Neonatal Ed 2018; 103: F221-F226.1 We complement the authors for this well conducted randomized trial on a very important subject of sedation while neonatal intubation. Having gone through the article, we would like to add the following.
    The intubations done were all non-emergent, with the mean gestational age being 27.6 (24-34) and 28.3 (24-36) weeks in both the groups respectively. It will be interesting to know what percentage of infants underwent Intubation, Surfactant administration, Extubation (INSURE)2 and placed back on nasal CPAP. As good respiratory drive is an essential prerequisite for nasal CPAP, there are concerns for sedation while attempting INSURE.
    The other concern is about the safety of both the drugs used in neonatal particularly in preterm population. There are reports of paradoxical stimulation of central nervous system including myoclonic movements associated with administration of midazolam.3 There is also evidence to suggest midazolam administration leading to increased NICU stay and adverse neurological events.4 The oscillometric blood pressure measurement recorded intermittently as in this study might not capture continuous invasive blood pressure changes.
    Finally, as the article very succinctly explained that the dosage of keta...

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  • CPAP and nasal injury

    Dilini I Imbulana and coworkers have published a good systematic review of nasal injuries in preterm infants receiving non-invasive respiratory support1. They included the early work by Robertson et al.2 but not the criticism from us3 or from the company selling the device4. At that time (1996), we had experiences of treatment of about 750 newborns with early versions of Infant Flow, including extremely preterm infants. We had not a single case of significant nasal injury. Imbulana et al. rightly write that it is important to chose correct size of nasal prongs (not too small). It is also crucial to avoid a hard pressure of the CPAP device on the nose. Moderate air leaks are acceptable. Several of the lesions published by Robertson and others are probable caused by attempts to avoid air leaks by a too tight connection between the CPAP device and the nose.
    Neonatal nurses from various hospitals and countries should meet face-to-face or via Skype to discuss and compare how they adapt CPAP devices to preterm newborns.
    Infant Flow was invented by the anaesthetists Drs Gunnar Moa and Kjell Nilsson at our hospital. We were the first paediatrician and neonatologist to use Infant Flow but we haven’t received any fees or other benefit for that.
    1. Imbulana DI, Manley BJ, Dawson JA, Davis PG, Owen LS. Nasal injury in preterm infants receiving non-invasive respiratory support: a systematic review. Archives of Disease in Childhood - Fetal and Neonatal...

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  • Combinations of subgroup analyses and impact on results

    We read with interest the follow up study by Thome and colleagues assessing neurodevelopmental outcomes of the extremely low birth weight (ELBW) infants from the Permissive Hypercapnia in Extremely Low Birthweight Infants (PHELBI) trial1.

    This study makes an important contribution to the evidence-base on the strategy of permissive hypercapnia for ELBW infants. It is a well-powered, multicentre trial and we commend the authors for the ambitious decision to include only intubated ELBW infants and also the use of a clinician-guided treatment protocol. While the methodology allows some systematic bias, there is strong external validity with a patient population representative of ‘real-life’ clinical practice.

    We question the choice to combine the subgroups with moderate and severe bronchopulmonary dysplasia (BPD) for statistical analysis. In Table 2, we note the non-significant p-value for the combined outcome of moderate/severe BPD of 0.30 and no reported p-values for the individual subgroups moderate BPD and severe BPD. Using the raw data provided in Table 2, we calculate a p-value for severe BPD as significant at 0.01, suggesting an increase.

    There is considerable clinical difference between patients with moderate BPD (requiring FiO2 <30% at 36 weeks or discharge) and those with severe BPD (requiring FiO2 ≥30% and/or positive pressure ventilation)2. Other than increased risk of mortality and respiratory disease, severity of BPD correlates with incr...

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  • Response to comments from Dr Mark W Davies and Drs Golumbek and Guidici

    Response to comment from Dr Mark W Davies:

    We agree that neurodevelopmental outcome may be an important outcome to measure following any neonatal surgery and would certainly welcome any study that reported this outcome in infants with gastroschisis. However following a rigorous consensus process as we have described, neurodevelopmental outcome was not selected as part of the core outcome set. We emphasise that the outcomes within the core outcome set are not the only outcomes that should be measured in future research but are the minimum recommended. Additional outcomes such as neurodevelopmental outcomes may of course be reported.

    Response to comment from Drs Golumbek and Guidici

    Drs Golumbek and Guidici are quite correct that characteristics of infants with gastroschisis, such as complexity of the condition at birth, may affect their prognosis. We are quite clear that this core outcome set should be used for observational studies which follow-up a cohort of infants based on these characteristics, as well as trials or observational studies which follow-up infants who have been managed using different surgical approaches. We agree that some of these outcomes are not specific to gastroschisis, but our aim was not to produce a core outcome set that had only gastroschisis specific outcomes within it, but one that contained the most important outcomes for infants with gastroschisis – some of which may apply equally to other infants. Growth at birth is not...

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  • To the editor

    Dear Nick Brown
    Editor in chief, Arch Dis Child Fetal Neonatal

    We read with interest the study titled “Development of a gastroschisis core outcome set” by Benjamin Saul Raywood Allin et al1, and we have several questions and comments.
    The aim of the authors is to design a core outcome set to be used in research in order to reduce outcome reporting heterogeneity and to help improve the clinical relevance of the research. The authors state that “Many gastroschisis studies investigate outcomes that are not relevant to patients or clinical practice”. However, they don´t clarify how they arrived to this hypothesis.
    This study has developed a gastroschisis core outcome set consisting of eight outcomes that are important to parents, people born with gastroschisis and clinicians.
    The eight outcomes are death, sepsis, growth, number of operations, time on parenteral nutrition, liver disease, number of severe gastrointestinal complications and quality of life. Regarding growth, it should be noticed that children born with gastroschisis are frequently intrauterine growth restricted, and therefore, this issue should be clarified - it is not always an outcome; gastrointestinal complications are also (up to 25% of gastroschisis population in some reports) a frequent component of the malformation itself, so this should be clarified when speaking of “complications”.
    In high income countries, adverse outcomes are related to the presence of complex gast...

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  • Development of a gastroschisis core outcome set: missed opportunity .

    Any surgery as a neonate carries increased risk of adverse neurodevelopmental outcomes and any neonatal study should include them. They are different from overall quality of life.

  • Practical advice on providing resuscitation of the neonate with an intact cord

    Physiologically based cord clamping stabilises cardiac output and reduces cerebrovascular injury in asphyxiated near-term lambs.

    Graeme R Polglase, Douglas A Blank, Samantha K Barton, Suzanne L Miller, Vanesa Stojanovska, Martin Kluckow, Andrew W Gill, Domenic LaRosa, Arjan B te Pas, Stuart B Hooper.

    Polglase and colleagues have shown that in near term asphyxiated lambs physiologically based cord clamping (PBCC) may be a more suitable option for the resuscitation of the asphyxiated newborn compared with the current standard practice of immediate cord clamping (ICC). This inevitably requires that the newborn remains close enough to its mother for the cord to remain intact. They showed evidence that brain injury was greatly reduced compared with ICC followed by resuscitation. This study in lambs suggests that delayed cord clamping may benefit most human infants, term and preterm, healthy and asphyxiated. Readers will wish to know how it is possible in practical terms to provide resuscitation at the side of the mother with an intact cord and this information is available from Katheria et al (1) and Batey et al (2).


    1. Katheria AC, Brown MK, Rich W and Arnell K (2017) Providing a Placental Transfusion in Newborns Who Need Resuscitation. Front. Pediatr. 5:1. doi: 10.3389/fped.2017.00001

    2. Batey N, et al. Arch Dis Child Educ Pract Ed 2017;102:235–238. doi:10.1136/archdischild-2016-312276