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.
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...
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 gastroschisis, which is not mentioned in this publication, and there are also several features associated with neonatal mortality (i.e., liver contained in the defect) that should be mentioned. We don’t believe that length of stay is a gastroschisis-specific variable associated with adverse outcomes; it is known that longer stays predict adverse outcomes in infants undergoing NICU admission.
The type of surgical approach is still being debated (as the authors stated) 2, 3, but the long-term outcomes are probably not related to this but, rather, to the type and size of the defect, the presence of complex gastroschisis, and the access to early intervention programs.
Twenty two parents completed all three phases of the Delphi process, most of them (64%) with children under five years of age at the time of the study. Recent publications alert about the association between gastroschisis and poorer verbal intelligence, an increased risk for poor performance on several aspects of attention, response inhibition and fine motor skills at school age 4, 5; therefore, it seems very important to have a larger sample of parents of school-aged children before considering that some aspects of their outcomes are not relevant.
We consider that high-quality observational studies and randomised controlled trials are required to assess the outcomes of gastroschisis patients, but those should definitively include more gastroschisis-specific variables, neurodevelopmental outcomes, and social behavior.
Respectfully,
Lidia B. Giúdici, MD
Pediatrician- Neonatologist
High Risk Newborn Follow Up Program Pedro de Elizalde Children's Hospital, Buenos Aires-Argentina
Postgraduate Neurodevelopment Specialization Director- Buenos Aires Medical College
Member of SEGUISIBEN- SIBEN (Iberoamerican Society of Neonatology)
Sergio G. Golombek, MD, MPH, FAAP
Professor of Pediatrics and Clinical Public Health
New York Medical College
Attending Neonatologist
Regional Neonatal Center-Maria Fareri Children's Hospital
Westchester Medical Center-Valhalla, NY 10595
President, SIBEN (Iberoamerican Society of Neonatology)
Ph # (914) 493-8488<tel:(914)%20493-8488>
FAX +1-914- 493-1005 Tel +1-914-493-8488
References
1- Allin BSR, Hall NJ, Ross AR, et al. Arch Dis Child Fetal Neonatal Ed Epub ahead of print: doi:10.1136/ archdischild-2017-314560
2- Charlesworth P, Ibiyinka A, Hammerton Ch et al. Preformed silos versus traditional abdominal wall closure in gastroschisis: 163 infants at a single institution. Eur J Pediatr Surg 2014; 24: 88-93.
3- Weil BR, Leysa CM, Rescorla FJ. The jury is still out: changes in gastroschisis management over the last decade are associated with both benefits and shortcomings. J Pediatr Surg 2012; 47: 119-124.
4- Giúdici L, Bokser V, Maricic M A, Golombek SG, Ferrario C., Babies born with gastroschisis and followed up to the age of six years faced long-term morbidity and impairments. Acta Paediatr. 2016; 105(6): 275-280.
5- Lap et al. Functional outcome at school age of children born with gastroschisis. Early Human Development 106–107 (2017) 47–52
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...
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 an outcome of postnatal treatment, therefore IUGR in this instance is not relevant, postnatal growth is clearly important whether or not an infants is small for gestational age at birth. 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.
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...
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 mechanics compared to mechanical ventilation using a PEEP of 6 cmH2O following a 30s Sustained Inflation (Tingay et al Ped Res 2014;75:288-94), later showing that this difference remained true irrespective of whether antenatal steroids or surfactant therapy was also used (Tingay et al Ped Res 2016;79:916-21). At the advice of one of the authors (SH) we then included an additional group managed with tidal inflations and a static PEEP of 8 cmH2O, as well as the sustained inflation and dynamic PEEP strategies, in our preterm lamb studies (Tingay et al Am J Respir Cell Mol Biol 2016;54:263-72). This study, demonstrated that both early and later (60 min life) aeration were more evenly distributed using a dynamic escalating/de-escalating PEEP strategy (maximum PEEP 20 cmH2O) than either static PEEP or an initial sustained inflation in preterm lambs without antenatal steroid or postnatal surfactant therapy. We replicated these differences between dynamic PEEP and static PEEP 8 cmH2O in a larger study of preterm lambs with antenatal steroid exposure (Tingay et al Am J Physiol Lung Cell Mol Physiol 2017;312:L32-L41).
An important finding of all these studies was that overexpansion was not noted with dynamic, transient PEEP during the respiratory transition and our strategy resulted in lower rate of airleak in lambs, unlike the study of Probyn (Ref 33).
More recently, we showed that transient PEEP exposure to 10 cmH2O, using a PEEP titration from 5 to 10 cmH2O, in 20 preterm infants <18 hours old resulted in improved lung volumes, without overexpansion, and that this volume could be maintained after PEEP was reduced in 65% of infants (Bhatia et al J Ped 2017;187:80-88), whilst acknowledging this study was performed in aerated lungs, it provides further support for the use of dynamic PEEP in the Delivery Room.
Of course whilst these studies only add to the body of literature regarding PEEP during the respiratory transition they must be considered within the context of the already large body of literature regarding PEEP level in the already aerated preterm lung. This includes, but is not limited to, the work of the Jobe group (for example Naik et al AJRCCM 2001;164:494-8), and Monkman et al (Crit Care Med 2004;32:2471-5).
The preclinical, and physiological clinical, literature regarding PEEP and CPAP in early preterm life is substantial. The variables influencing the interplay between volume state and applied pressure during the respiratory transition suggest that a dynamic approach to PEEP will be needed.
Tessa Martherus1, André Oberthuer2, Janneke Dekker1, Stuart B Hooper3,4, Erin V McGillick3,4, Angela Kribs2, Arjan B te Pas1
1 Department of Paediatrics, Leiden University Medical Center, Leiden, The Netherlands
2 Department of Neonatology, Children’s Hospital University of Cologne, Cologne, Germany
3 The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Australia
4 Department of Obstetrics and Gynaecology, Monash University, Melbourne, Australia
We thank the author for his interest in our review and for acknowledging that it is timely. In our review we cover the support of spontaneous breathing infants at birth with CPAP and discuss what CPAP pressures should be used. The clinical paper the author is referring to is beyond the scope of this review as the infants were 12-18 hours old and this is a completely different situation dealing with different pulmonary characteristics. In our opinion, mechanical ventilation and PEEP in intubated newborns has very little to contribute to this discussion other than indicating how end-expiratory pressures can improve lung aeration and that at high levels they have a negative impact on pulmonary blood flow and venous return. These points were adequately covered in the references cited and we also note that none of the author's papers report how high PEEP levels impact on pulmonary blood flow....
Tessa Martherus1, André Oberthuer2, Janneke Dekker1, Stuart B Hooper3,4, Erin V McGillick3,4, Angela Kribs2, Arjan B te Pas1
1 Department of Paediatrics, Leiden University Medical Center, Leiden, The Netherlands
2 Department of Neonatology, Children’s Hospital University of Cologne, Cologne, Germany
3 The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Australia
4 Department of Obstetrics and Gynaecology, Monash University, Melbourne, Australia
We thank the author for his interest in our review and for acknowledging that it is timely. In our review we cover the support of spontaneous breathing infants at birth with CPAP and discuss what CPAP pressures should be used. The clinical paper the author is referring to is beyond the scope of this review as the infants were 12-18 hours old and this is a completely different situation dealing with different pulmonary characteristics. In our opinion, mechanical ventilation and PEEP in intubated newborns has very little to contribute to this discussion other than indicating how end-expiratory pressures can improve lung aeration and that at high levels they have a negative impact on pulmonary blood flow and venous return. These points were adequately covered in the references cited and we also note that none of the author's papers report how high PEEP levels impact on pulmonary blood flow.
Response to The secret sauce: secrets of high performing neonatal intensive care units
Soghier and Short highlight the importance of local contextual factors in determining the success of improvement initiatives in neonatal units. They draw attention to a number of qualitatively assessed factors, many of which are prefixed by the adjectives “effective”, “active” and, “strong” reflecting the importance of leadership and team culture in effective organisations.
Whilst contextual factor surveys might have a place in identifying the readiness of teams to undertake active improvement, they do little to assist organisations in improving their own readiness. The features of good healthcare leadership and team culture are not readily measured, and healthcare professionals in the UK have little or no training in the attitudes and skills necessary for leadership in quality improvement.
The Institute for Healthcare Improvement has attempted to describe the features of a high quality healthcare organisation in some detail (1). The British Association of Perinatal Medicine has recently produced Quality Indicators relating to structures and processes relevant to Quality and Patient Safety in the context of current neonatal care in the UK (2), which it is hoped will create a basis for units to develop “quality-readiness”.
There is reason to believe that collaboration across centres might add momentum to quality improvement (3). The UK, which has good access to...
Response to The secret sauce: secrets of high performing neonatal intensive care units
Soghier and Short highlight the importance of local contextual factors in determining the success of improvement initiatives in neonatal units. They draw attention to a number of qualitatively assessed factors, many of which are prefixed by the adjectives “effective”, “active” and, “strong” reflecting the importance of leadership and team culture in effective organisations.
Whilst contextual factor surveys might have a place in identifying the readiness of teams to undertake active improvement, they do little to assist organisations in improving their own readiness. The features of good healthcare leadership and team culture are not readily measured, and healthcare professionals in the UK have little or no training in the attitudes and skills necessary for leadership in quality improvement.
The Institute for Healthcare Improvement has attempted to describe the features of a high quality healthcare organisation in some detail (1). The British Association of Perinatal Medicine has recently produced Quality Indicators relating to structures and processes relevant to Quality and Patient Safety in the context of current neonatal care in the UK (2), which it is hoped will create a basis for units to develop “quality-readiness”.
There is reason to believe that collaboration across centres might add momentum to quality improvement (3). The UK, which has good access to national neonatal data and a mature benchmarking system, is well set up for collaborative neonatal quality improvement. Professional organisations now need to actively promote collaboration by bringing together clinical leaders focused on excellence, encouraging neonatal units to work together, and facilitating a national community of learning. This might be the missing link to producing a step change in the quality of neonatal care.
1. Frankel A, Haraden C, Federico F, Safe LJAF, White EC. A Framework for Safe, Reliable, and Effective Care. Cambridge, MA; 2017.
2. The British Association of Perinatal Medicine. Neonatal Service Quality Indicators. London; 2017. https://www.bapm.org/NSQI
3. ØVretveit J, Bate P, Cleary P, Cretin S, Gustafson D, McInnes K, et al. Quality collaboratives: lessons from research. Qual Saf Health Care [Internet]. 2002;11(4):345–51. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12468695%5Cnhttp://www.pubmedcentral....
I agree with the authors that the question of end-expiratory pressure at birth needs to focus on CPAP. As the authors highlight, the entirety of the preclinical literature has been performed in mechanically ventilated, intubated and sedated animals, and the role of PEEP on pulmonary blood flow during the actual respiratory transition is yet to be investigated. Neither of these limitations are insurmountable and I am confident the authors can rectify this gap in knowledge.
The rapidly changing cardiorespiratory events immediately following birth and the concerns regarding with too low and too high a PEEP further emphasise the need for a dynamic approach to PEEP levels.
I wish to comment about the outcomes you have selected for your study on gastroschisis and in particular caution against the use of 'primary closure' as an outcome at all. There are a number of reasons for this. Firstly, implicit in the use of primary closure as an outcome is a belief that it is either a good or bad thing. The literature would not support that either delayed closure or primary closure is superior, therefore it is impossible to know how to interpret a higher (or lower) rate of primary closure following either Caesarian section or vaginal delivery. Is a higher rate of primary closure good or bad? Secondly, the increasing use by paediatric surgeons of the preformed silo to manage return of the visceral contents to the abdominal cavity means that the closure technique may be prescribed rather than one that is dependent on other factors (such as mode of delivery). Its relevance therefore as an outcome is highly questionable.
I note also that you encountered 'differences in definition of outcomes, choice of outcome measures and variation in reporting methods'. Such difficulties can be a real challenge in the context of a meta-analysis and preclude accurate evidence synthesis. One proposed way to address this challenge is the development and use of a Core Outcome Set. A Core Outcome Set is a set of outcomes that has been derived through consensus methodology across stakeholder groups as being the most important outcomes to measure in re...
I wish to comment about the outcomes you have selected for your study on gastroschisis and in particular caution against the use of 'primary closure' as an outcome at all. There are a number of reasons for this. Firstly, implicit in the use of primary closure as an outcome is a belief that it is either a good or bad thing. The literature would not support that either delayed closure or primary closure is superior, therefore it is impossible to know how to interpret a higher (or lower) rate of primary closure following either Caesarian section or vaginal delivery. Is a higher rate of primary closure good or bad? Secondly, the increasing use by paediatric surgeons of the preformed silo to manage return of the visceral contents to the abdominal cavity means that the closure technique may be prescribed rather than one that is dependent on other factors (such as mode of delivery). Its relevance therefore as an outcome is highly questionable.
I note also that you encountered 'differences in definition of outcomes, choice of outcome measures and variation in reporting methods'. Such difficulties can be a real challenge in the context of a meta-analysis and preclude accurate evidence synthesis. One proposed way to address this challenge is the development and use of a Core Outcome Set. A Core Outcome Set is a set of outcomes that has been derived through consensus methodology across stakeholder groups as being the most important outcomes to measure in research related to a condition. The concept being that if all studies of a condition use a core outcome set then it is much easier to perform meta-analysis reliably. Other benefits include being more certain that the most important outcomes (as defined by a range of stakeholder groups) are being measured and reported.
We have recently developed a core outcome set for gastroschisis (Allin et al Arch Dis Child Fetal Neonatal Ed 2018 doi: 10.1136/archdischild-2017-314560) and would like to bring this to your and other researchers' attention. We believe it may help with some of the difficulties you have encountered in evidence synthesis and will provide a framework for other researchers when selecting which outcomes to measure in future studies of infants with gastroschisis.
We would like to thank Dr. Hutchon for his considered letter and for highlighting a number of important points. We very much acknowledge his experience in the area of cord management at the time of delivery and his ongoing endeavours to advocate for appropriate cord management at the time of delivery(1). He correctly notes that there is no current formal policy for cord management at delivery for term newborn infants in our institution, which undoubtedly results in variability in practice. In a recently completed prospective study evaluating cardiac output in healthy term infants, we have noted that approximately one third of infants had early cord clamping and two thirds some form of placental transfusion, either as delayed or milking. Whilst we cannot be certain or draw any definitive inferences, it is likely that this same variability exits in our cohort of patients. The point related to ‘immediate transfer’ to the resuscitaire may be somewhat misleading. This relates to once the cord is clamped, and not that the cord was immediately clamped in each case(2). We acknowledge that this terminology may be confusing, and therefore cannot concur that our results relate to early cord clamping alone. It is also important to highlight that all our newborns were spontaneously breathing at delivery and did not require any assistance with adaptation.
He makes a very valid comparison with oxygen saturation values in term infants highlighti...
We would like to thank Dr. Hutchon for his considered letter and for highlighting a number of important points. We very much acknowledge his experience in the area of cord management at the time of delivery and his ongoing endeavours to advocate for appropriate cord management at the time of delivery(1). He correctly notes that there is no current formal policy for cord management at delivery for term newborn infants in our institution, which undoubtedly results in variability in practice. In a recently completed prospective study evaluating cardiac output in healthy term infants, we have noted that approximately one third of infants had early cord clamping and two thirds some form of placental transfusion, either as delayed or milking. Whilst we cannot be certain or draw any definitive inferences, it is likely that this same variability exits in our cohort of patients. The point related to ‘immediate transfer’ to the resuscitaire may be somewhat misleading. This relates to once the cord is clamped, and not that the cord was immediately clamped in each case(2). We acknowledge that this terminology may be confusing, and therefore cannot concur that our results relate to early cord clamping alone. It is also important to highlight that all our newborns were spontaneously breathing at delivery and did not require any assistance with adaptation.
He makes a very valid comparison with oxygen saturation values in term infants highlighting the differences in oxygen saturation values between the Australian (3)and Leiden studies(4), attributing this difference to the impact of delayed cord clamping. It is interesting to note that there was a higher degree of bradycardia less than 80bpm in the Leiden cohort who received delayed cord clamping(4). A recent single centre study performed in Melbourne by Blank et al provides even greater clarity on respiratory adaptation(5). They evaluated similar respiratory variables to our measurements in a cohort of term infants, delivered both vaginally and by caesarean section. They did not identify any difference in respiratory variables between spontaneously breathing term infants based on mode of delivery. This is interesting when one considers that their hospital policy mandates caesarean delivered babies have immediate clamping and vaginally delivered have delayed clamping performed. This would suggest that in healthy term infants who do not require any respiratory support at birth, the timing of cord clamping results in no obvious difference in immediate respiratory variables over the first 10 mins of life. However this does not imply that delayed cord clamping has no immediate benefits on babies who may need support during this period of adaptation, and future work in this area is certainly warranted.
Eugene Dempsey and Daragh Finn
References
1. Hutchon D, Bettles N. Motherside care of the term neonate at birth. Matern Health Neonatol Perinatol. 2016;2:5.
2. Finn D, De Meulemeester J, Dann L, Herlihy I, Livingstone V, Boylan GB, et al. Respiratory adaptation in term infants following elective caesarean section. Arch Dis Child Fetal Neonatal Ed. 2018;103(5):F417-F21.
3. Dawson JA, Kamlin CO, Vento M, Wong C, Cole TJ, Donath SM, et al. Defining the reference range for oxygen saturation for infants after birth. Pediatrics. 2010;125(6):e1340-7.
4. Smit M, Dawson JA, Ganzeboom A, Hooper SB, van Roosmalen J, te Pas AB. Pulse oximetry in newborns with delayed cord clamping and immediate skin-to-skin contact. Arch Dis Child Fetal Neonatal Ed. 2014;99(4):F309-14.
5. Blank DA, Gaertner VD, Kamlin COF, Nyland K, Eckard NO, Dawson JA, et al. Respiratory changes in term infants immediately after birth. Resuscitation. 2018;130:105-10.
Finn et al (1) describe respiratory adaptation in term infants following elective caesarean section and the other intervention of early cord clamping(2). Although the timing of cord clamping was not documented and there is no policy for delayed cord clamping at Cork University Maternity Hospital, the authors state that the neonates were transferred immediately after birth to a Panda Resuscitator and other non-invasive monitoring equipment, thus requiring early cord clamping in all infants studied.
The aim of the study was to define newborn physiological ventilation parameters (respiratory rate (RR), TV, end-tidal carbon dioxide (EtCO2)) over the first minutes of life in healthy-term infants following ECS, in the same way that Dawson and colleagues(3) produced centile charts in 2010 detailing the normalisation of oxygen saturations over time during newborn adaptation after normal vaginal birth. All the babies studied by Dawson et al also experienced a transition of the circulatory system which was interrupted by early cord clamping but, in a study in 2014 by Smit et al(4), in which cord clamping was delayed by at least one minute, they showed that cord clamping had resulted in a lower oxygen saturation during the first few minutes after birth. The median SpO2 of the babies experiencing early cord clamping was 11, 7 and 4% lower at minute 1, 2 and 3 respectively. All these babies already had the advantage of a physiological preparation through the mechanical and hor...
Finn et al (1) describe respiratory adaptation in term infants following elective caesarean section and the other intervention of early cord clamping(2). Although the timing of cord clamping was not documented and there is no policy for delayed cord clamping at Cork University Maternity Hospital, the authors state that the neonates were transferred immediately after birth to a Panda Resuscitator and other non-invasive monitoring equipment, thus requiring early cord clamping in all infants studied.
The aim of the study was to define newborn physiological ventilation parameters (respiratory rate (RR), TV, end-tidal carbon dioxide (EtCO2)) over the first minutes of life in healthy-term infants following ECS, in the same way that Dawson and colleagues(3) produced centile charts in 2010 detailing the normalisation of oxygen saturations over time during newborn adaptation after normal vaginal birth. All the babies studied by Dawson et al also experienced a transition of the circulatory system which was interrupted by early cord clamping but, in a study in 2014 by Smit et al(4), in which cord clamping was delayed by at least one minute, they showed that cord clamping had resulted in a lower oxygen saturation during the first few minutes after birth. The median SpO2 of the babies experiencing early cord clamping was 11, 7 and 4% lower at minute 1, 2 and 3 respectively. All these babies already had the advantage of a physiological preparation through the mechanical and hormonal adjustments that occur during labour and vaginal delivery, so it is quite possible early cord clamping may have an even greater effect on the circulation and respiratory function after elective CS. Animal studies suggest that the effect of early cord clamping is less if respiration and the pulmonary circulation is established. No doubt many of these babies will have already taken their first breath before the cord was clamped, but we do not know how big an effect early clamping had on the overall results. Thus this study only contributes to our understanding of respiratory adaption of the term neonate following elective caesarean section and early cord clamping. ILCOR and NICE both recommend delayed cord clamping at the birth of all uncompromised term neonates. All babies born by elective CS should have delayed clamping if these guidelines are being followed and it is our understanding of the respiratory adaption of these babies which is still needed.
References
1. Finn D, De Meulemeester J, Dann L, et al Respiratory adaptation in term infants following elective caesarean section Archives of Disease in Childhood - Fetal and Neonatal Edition 2018;103:F417-F421.
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.
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.
Show MoreThe 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...
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...
Show MoreDear 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...
Show MoreTessa Martherus1, André Oberthuer2, Janneke Dekker1, Stuart B Hooper3,4, Erin V McGillick3,4, Angela Kribs2, Arjan B te Pas1
1 Department of Paediatrics, Leiden University Medical Center, Leiden, The Netherlands
2 Department of Neonatology, Children’s Hospital University of Cologne, Cologne, Germany
3 The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Australia
4 Department of Obstetrics and Gynaecology, Monash University, Melbourne, Australia
We thank the author for his interest in our review and for acknowledging that it is timely. In our review we cover the support of spontaneous breathing infants at birth with CPAP and discuss what CPAP pressures should be used. The clinical paper the author is referring to is beyond the scope of this review as the infants were 12-18 hours old and this is a completely different situation dealing with different pulmonary characteristics. In our opinion, mechanical ventilation and PEEP in intubated newborns has very little to contribute to this discussion other than indicating how end-expiratory pressures can improve lung aeration and that at high levels they have a negative impact on pulmonary blood flow and venous return. These points were adequately covered in the references cited and we also note that none of the author's papers report how high PEEP levels impact on pulmonary blood flow....
Show MoreResponse to The secret sauce: secrets of high performing neonatal intensive care units
Soghier and Short highlight the importance of local contextual factors in determining the success of improvement initiatives in neonatal units. They draw attention to a number of qualitatively assessed factors, many of which are prefixed by the adjectives “effective”, “active” and, “strong” reflecting the importance of leadership and team culture in effective organisations.
Whilst contextual factor surveys might have a place in identifying the readiness of teams to undertake active improvement, they do little to assist organisations in improving their own readiness. The features of good healthcare leadership and team culture are not readily measured, and healthcare professionals in the UK have little or no training in the attitudes and skills necessary for leadership in quality improvement.
The Institute for Healthcare Improvement has attempted to describe the features of a high quality healthcare organisation in some detail (1). The British Association of Perinatal Medicine has recently produced Quality Indicators relating to structures and processes relevant to Quality and Patient Safety in the context of current neonatal care in the UK (2), which it is hoped will create a basis for units to develop “quality-readiness”.
There is reason to believe that collaboration across centres might add momentum to quality improvement (3). The UK, which has good access to...
Show MoreI agree with the authors that the question of end-expiratory pressure at birth needs to focus on CPAP. As the authors highlight, the entirety of the preclinical literature has been performed in mechanically ventilated, intubated and sedated animals, and the role of PEEP on pulmonary blood flow during the actual respiratory transition is yet to be investigated. Neither of these limitations are insurmountable and I am confident the authors can rectify this gap in knowledge.
The rapidly changing cardiorespiratory events immediately following birth and the concerns regarding with too low and too high a PEEP further emphasise the need for a dynamic approach to PEEP levels.
I wish to comment about the outcomes you have selected for your study on gastroschisis and in particular caution against the use of 'primary closure' as an outcome at all. There are a number of reasons for this. Firstly, implicit in the use of primary closure as an outcome is a belief that it is either a good or bad thing. The literature would not support that either delayed closure or primary closure is superior, therefore it is impossible to know how to interpret a higher (or lower) rate of primary closure following either Caesarian section or vaginal delivery. Is a higher rate of primary closure good or bad? Secondly, the increasing use by paediatric surgeons of the preformed silo to manage return of the visceral contents to the abdominal cavity means that the closure technique may be prescribed rather than one that is dependent on other factors (such as mode of delivery). Its relevance therefore as an outcome is highly questionable.
I note also that you encountered 'differences in definition of outcomes, choice of outcome measures and variation in reporting methods'. Such difficulties can be a real challenge in the context of a meta-analysis and preclude accurate evidence synthesis. One proposed way to address this challenge is the development and use of a Core Outcome Set. A Core Outcome Set is a set of outcomes that has been derived through consensus methodology across stakeholder groups as being the most important outcomes to measure in re...
Show MoreWe would like to thank Dr. Hutchon for his considered letter and for highlighting a number of important points. We very much acknowledge his experience in the area of cord management at the time of delivery and his ongoing endeavours to advocate for appropriate cord management at the time of delivery(1). He correctly notes that there is no current formal policy for cord management at delivery for term newborn infants in our institution, which undoubtedly results in variability in practice. In a recently completed prospective study evaluating cardiac output in healthy term infants, we have noted that approximately one third of infants had early cord clamping and two thirds some form of placental transfusion, either as delayed or milking. Whilst we cannot be certain or draw any definitive inferences, it is likely that this same variability exits in our cohort of patients. The point related to ‘immediate transfer’ to the resuscitaire may be somewhat misleading. This relates to once the cord is clamped, and not that the cord was immediately clamped in each case(2). We acknowledge that this terminology may be confusing, and therefore cannot concur that our results relate to early cord clamping alone. It is also important to highlight that all our newborns were spontaneously breathing at delivery and did not require any assistance with adaptation.
He makes a very valid comparison with oxygen saturation values in term infants highlighti...
Show MoreFinn et al (1) describe respiratory adaptation in term infants following elective caesarean section and the other intervention of early cord clamping(2). Although the timing of cord clamping was not documented and there is no policy for delayed cord clamping at Cork University Maternity Hospital, the authors state that the neonates were transferred immediately after birth to a Panda Resuscitator and other non-invasive monitoring equipment, thus requiring early cord clamping in all infants studied.
The aim of the study was to define newborn physiological ventilation parameters (respiratory rate (RR), TV, end-tidal carbon dioxide (EtCO2)) over the first minutes of life in healthy-term infants following ECS, in the same way that Dawson and colleagues(3) produced centile charts in 2010 detailing the normalisation of oxygen saturations over time during newborn adaptation after normal vaginal birth. All the babies studied by Dawson et al also experienced a transition of the circulatory system which was interrupted by early cord clamping but, in a study in 2014 by Smit et al(4), in which cord clamping was delayed by at least one minute, they showed that cord clamping had resulted in a lower oxygen saturation during the first few minutes after birth. The median SpO2 of the babies experiencing early cord clamping was 11, 7 and 4% lower at minute 1, 2 and 3 respectively. All these babies already had the advantage of a physiological preparation through the mechanical and hor...
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