Displaying 1-9 letters out of 568 published
Authors' response: Perinatal Outcomes; Marlow et al 2014;99:F181-8
We are grateful to Dr Ehrhardt for his response to our recent paper.(1) It is certainly true that the populations compared are indeed very different, which generally makes any such comparison fraught with potential problems in interpretation. However, we would respectfully point out that we made some allowance for this in our analysis of place of booking and outcomes. This quite clearly shows advantage to women booking in Level 3 Services, compared to those booking in Level 2 services whether or not they were transferred (aOR: 0.79 (0.63; 0.98)).
In a related paper using more recent national data and instrumental variables using the nearest hospital to the mother's residence to describe the base populations, we also come to the same conclusion for this group of extremely preterm births.(2)
Although not perfect corrections for a complex situation these two findings provide some reassurance that our conclusions are valid.
Yours sincerely Neil Marlow
1. Marlow N, Bennett C, Draper ES, et al. Perinatal outcomes for extremely preterm babies in relation to place of birth in England: The EPICure 2 Study. Archives of Disease in Childhood Fetal and Neonatal Edition 2014;99:F181-8
2. Watson SI, Arulampalam W, Petrou S, et al. The effects of designation and volume of neonatal care on mortality and morbidity outcomes of very preterm infants in England: retrospective population- based cohort study. BMJ Open 2014;4(7):e004856.
Conflict of Interest:
Author of original paper
Answer to: "Physiolgical transition ?"
Response to "Physiological transition ?"
Thank you for your response to our research "Non-invasive measurements of ductus arteriosus flow directly after birth".
We agree with Dr. Hutchon that a caesarian section can influence the respiratory transition of a newborn infant. As such, our results reflect the transition after elective caesarian section with cord clamping within 1 minute after birth, which we have indicated is a limitation of our study as stated in the Discussion section of our manuscript. However, as cord clamping was delayed between 30-60 s after birth, most newborns will have commenced breathing before the cord was clamped. While many guidelines suggest a fixed time interval of 1-3 minutes between birth and cord clamping, this is not physiological and is only relevant to individual infants because most infants will have commenced breathing within this time. We agree that infants that did not started breathing sufficiently before cord clamping could have had a less efficient transition, but our small sample size prohibits a more detailed subgroup analysis. However, as all of these infants had a normal "clinical" transition and did not require respiratory support or any other specialized medical care, we feel that the potential influence of cord clamping before the start of breathing had no significant clinical impact. With regard to the WHO advice, the observations from Bhatt et al. show that the timing of cord clamping is probably less important than the occurrence of breathing before the cord is clamped.(1) It would be interesting to compare the transition of neonates after vaginal delivery to our results. However, no data within the first 10 minutes after vaginal delivery is present as our report is the first to assess hemodynamic changes during this time frame. This study may therefore be regarded as a starting point for future research on hemodynamic changes directly after birth.
As we have described in a previous publication, aeration of the lung and the consequent rise in preload is most likely responsible for the increase in left ventricular output (LVO).(2) The increase in preload will cause a pressure gradient to exist over the Ductus Arteriosus (DA) and foramen ovale (FO). As Dr. Hutchon suggests the resulting shunt over the FO could explain differences between LVO and right ventricular output (RVO). However, we must stress that the simple mathematical calculation of adding or subtracting mean blood flows and outputs from a group of infants, which were measured using echocardiography at different time points is not a legitimate way of making comparisons. The values stated in our manuscript are mean values and although they were all measured within a small time range, it is not possible to make these measurements simultaneously. As these parameters are very dynamic and change over time, ideally they should be measured simultaneously and comparisons should be made in individual infants rather between groups means. Furthermore, Doppler derived measurements of absolute volume are based on several assumptions and cardiac output can range from 150 ml/kg/min to 273 ml/kg/min for LVO and from 200 to 310 ml/kg/min for RVO in term neonates depending on the site of measurement, the vascular diameter and Doppler method used.(3) As such we believe that the calculation of shunting across the FO as done by Dr. Hutchon is based on too many assumptions for any valid conclusions to be drawn. We consider that our figures are neither an anomaly nor a sign of a disrupted transitional circulation, but merely reflect the suboptimal assessment of absolute volumes with echocardiography.
This is the main reason that we did not focus on the absolute differences between LVO and RVO at the described time points. Instead we used the Doppler derived measurements to assess differences over time during the first 10 minutes after birth in LVO, RVO and blood flow shunt over the DA. Furthermore, we calculated the ratio between DA right-to-left vs. left-to-right flow based on the velocity time integral of the flow patterns. As this is a dimensionless parameter that is not influenced by assumptions or inaccuracies in the measurement of vessel diameter, it is more appropriate to use for investigations into the hemodynamic transition.
The matter of whether left-to-right shunting across the FO is a normal physiological process is an interesting point and one that hasn't really been addressed previously, mostly because it was previously considered to be a one way valve. Nevertheless, as the two ventricles act as two independent pumps working at different outputs throughout fetal life, we consider that it is unrealistic to expect that the ventricles will immediately synchronize their outputs at birth. Instead we believe that there will be a period of adjustment during the immediate newborn period and theoretically bidirectional flows in both the FO and the DA would allow both ventricular outputs to come into balance without triggering systemic hypotension or pulmonary hypertension.
(1) Bhatt S, Alison BJ, Wallace EM, Crossley KJ, Gill AW, Kluckow M, et al. Delaying cord clamping until ventilation onset improves cardiovascular function at birth in preterm lambs. J Physiol 2013;591:2113 -26.
(2) van Vonderen JJ, Roest AA, Siew ML, Blom NA, van Lith JM, Walther FJ, et al. Noninvasive measurements of hemodynamic transition directly after birth. Pediatr Res 2014;75:448-52.
(3) de Waal KA. The methodology of Doppler-derived central blood flow measurements in newborn infants. Int J Pediatr 2012;2012:680162.
Conflict of Interest:
Reliability of NNAP's RoP screening data
We are sorry to hear that colleagues at the Royal Free Hospital felt that our analysis of the data they provided did not reflect the realities of what is happening in their neonatal unit.
We have already made significant changes to the processes for the 2013 data, which is expected to be published this October. NNAP now includes entries in either of the locations within the badger system ("daily data" or "ad hoc forms") as indicating that an ROP screen took place. Furthermore, we have worked with the software supplier so that within the current version of the software an entry in the daily data to indicate that an ROP screen took place now automatically opens an ad hoc form, where the rest of the details of the ROP screen can be entered.
We hope that these measures, and others such as the inclusion of post discharge ROP screens conducted at the correct time, will help NNAP and its participant units to highlight good practice, as well as identifying any units where adherence to national guidance is not yet complete.
We also agree that training users in data entry, ensuring staff understand the significance of data entry and reviewing data prior to its use for national audit, is crucial for the audit to be effective.
Finally, it is good to hear that the unit is reviewing its processes in response to the NNAP findings, as the main aim of the audit is to ensure best practice is shared to improve care for newborns.
Conflict of Interest:
Clinical Lead, NNAP
Reliability of NNAP's RoP screening data
The letter by Neil Finer and others raises important questions around quality and completeness of data used for national benchmarking.
The authors criticise the quality of NNAP data used in the published 2012 report. They show in one unit where there were inaccuracies due to data not being entered into the Badger system. They give examples of how the Badger system possibly contributed to the problem by not alerting users adequately to missing data.
The NNAP project gives the neonatal community in UK a unique opportunity to analyse whole population data. I hope these reported problems with NNAP data are not seen as a reason to stop national audit and benchmarking but as a reminder of the need to take seriously the collection of better data. It is inevitably an iterative process and NNAP is continuing to evolve and improve. The neonatal community must continue to support the very important role of a national benchmarking project.
The requirements of NNAP are published and units should have in place systems to ensure timely collection of important data.
Clevermed is committed to working with users, and with NNAP, to assist in the collection of data that are complete and of good quality, as well ensuring timely and correct downloads.
Since 2012 the 'idiosyncrasies' referred to in the letter have already been addressed within the new version of the software (BadgerNet) and further improvements are due for release. There are also many more lists, dashboards and reports that help users check the quality and completeness of their data. I believe that the quality and completeness of ROP screening data within the system has already improved significantly since 2012.
More than 80% of units have changed (at no charge) to the new version of the software and Clevermed aims to complete the migration by the end of 2014 when the older Badger 3 will no longer be supported.
Conflict of Interest:
Dr Andrew Lyon works with, and receives payment from, Clevermed Ltd.
An early PDA is not always a benign entity
We read with interest the article by Rolland et al regarding a retrospective natural history study of the PDA in a cohort of preterm infants in a unit which conservatively managed the presence of a PDA after 24 hours(1). We have concerns about the data analysis and the conclusions drawn. In particular we question the decision to exclude infants who died within the first 72 hrs and the subsequent exclusion of infants who died, due to inability to determine the date of PDA closure. Out of the total cohort (103 infants) 12 died and were excluded in the first 72 hrs and a further 13 subsequently died and were excluded meaning that almost 25% of the cohort died without having their ductal status documented. As the authors themselves acknowledge, a significant number of these infants died from complications that may be related to a PDA, including pulmonary haemorrhage, intraventricular haemorrhage, unresponsive respiratory or multisystem failure and NEC. It is misleading to exclude these from the natural history cohort and this approach by other authors in the past has led to a potential misrepresentation of the harm that may occur as a result of a persisting DA. There are several published natural history series showing significant and strong associations with morbidity and mortality if all-cause mortality is left in the cohort for analysis purposes(2,3). Of the total group of 103 infants in this study only 59 (57%) have certain documentation of ductal closure. The balance of 44 infants either died (26 infants) or did not have spontaneous closure documented using the gold standard of an echocardiogram. 7 infants had a persisting PDA at discharge which is of itself not a benign outcome with potential for increased mortality in the first year(2) and a possible requirement for surgical closure. If it is assumed that all of the unaccounted for patients had a PDA, the spontaneous closure rate is actually only 57% - 16% lower than that reported in the conclusion of this paper of 73%. The premise of Rolland et al is that early ductal shunting is not important, whereas work by our group suggests that the first 24-48 hours may be the most important time for ductal related morbidity. Lack of early assessment of the hemodynamic effects of a PDA in the first 72 hrs of life often results in failure to recognise the association between early PDA and morbidity/mortality. There is clear benefit to early/prophylactic treatment of a significant PDA including reduced pulmonary haemorrhage and intraventricular haemorrhage(4). We have recently published a trial of targeted early treatment vs placebo demonstrating reduction in pulmonary haemorrhage and reduced later treatment of PDA(5). Benefits from later treatment after 3 days are less clear and as identified by many authors should be the subject of well performed RCT's. Performing a cohort study and excluding infants who have uncertain ductal status and suffer an adverse outcome is problematic. An alternative conclusion to the data presented is that a significant number of infants in this cohort died from potential duct related complications such as pulmonary haemorrhage and that earlier identification and treatment may have avoided this. Concluding from the data presented that the exposure to the risk of therapeutic intervention to close a PDA is not warranted based on spontaneous closure rates of a selected surviving sub-group is not justified.
References: 1] Rolland A, Shankar-Aguilera S, Diomand? D et al. Arch Dis Child Fetal Neonatal Ed Published Online First: 28 August 2014 doi:10.1136/archdischild-2014- 306339 2] Noori S. McCoy M. Friedlich P et al. Failure of ductus arteriosus closure is associated with increased mortality in preterm infants. Pediatrics 2009;123(1):e138-44. 3] Sellmer A, Vandborg Bjerre J,T+Rahbek Schmidt M et al. Morbidity and mortality in preterm neonates with patent ductus arteriosus on day 3. Arch Dis Child Fetal Neonatal Ed 2013 Nov;98(6):F505-10. 4] Fowlie PW, Davis PG, McGuire W. Prophylactic intravenous indomethacin for preventing mortality and morbidity in preterm infants.[Update of Cochrane Database Syst Rev. 2002;(3):CD000174; PMID: 12137607]. Cochrane Database Syst Rev 2010;CD000174. 5] Kluckow M, Jeffery M, Gill A et al. A randomised placebo-controlled trial of early treatment of the patent ductus arteriosus. Arch Dis Child Fetal Neonatal Ed 2014;99:F99-F104.
Conflict of Interest:
Fresh frozen plasma use in the NICU: a prospective, observational, multicentred study
We read with interest the recent publication by Motta and colleagues (1). Their data pertaining to use of fresh frozen plasma (FFP) in the neonatal intensive care unit are helpful.
The British Committee for Standards in Haematology transfusion guidelines (2) suggest that any neonates with significant coagulopathy [e.g. prothrombin time (PT)/activated partial thromboplastin time (APTT) ratio >1.5] and significant risk of bleeding (e.g. preterm and/or intubated, previous periventricular haemorrhage), FFP is indicated. We believe that this practice may lead to over-transfusion of FFP.
We have recently published data pertaining to the extremely premature neonatal population (n = 183) born < 27 weeks' gestation on day 1 of life (3). In this large patient cohort, we observed similar clotting times to those reported by Motto and co-workers(Table 3) (1) in their similar but smaller patient population. In our cohort, median (range 25th-75th percentile) prothrombin time (PT) and activated partial thromboplastin time (APTT) values were 20.2 (17.8-24.1) and 67.4 (56.3-88.4) seconds, respectively.
Unfortunately, timing of both cranial sonography and specific laboratory assessments of haemostasis were not described by Motto et al (1). Coagulation tests were performed pre FFP transfusion, only 42% of which occurred in first 3 days of life, with remainder occurring at later postnatal age. Most intraventricular haemorrhage occurs within first 72 hours of life. The timing of blood sampling may influence results of coagulation parameters, as coagulation values change with gestational age (4). The association/lack thereof between IVH and coagulation values is difficult to establish given lack of clarity regarding timing of both events.
We agree with the authors that FFP should be used cautiously given paucity of evidence for effectiveness of these transfusions. Given that extremely premature infants have median coagulation values > 1.5 ratio, review of FFP transfusion guidelines is warranted, as many additional infants may have had FFP without good indication.
Elaine Neary, MB, BCh, BAO, BA, MSc, MRCPI, PGDIP (1)
Fionnuala Ni Ainle, MB, BCh, BAO, MRCPI, FRCPath, PhD (2)
Melanie Cotter, MB, BCh, BAO, DCH, MSc, FRCPI, FRCPath, MD (2)
Naomi McCallion, MB, BCh, BAO, MRCPI, MD (1)
(1)Department of Paediatrics, Rotunda Hospital, Dublin, Ireland
(2)Department of Haematology, Rotunda Hospital, Dublin, Ireland
1. Motta M, Del Vecchio A, Perrone B, Ghirardello S, Radicioni M. Fresh frozen plasma use in the NICU: a prospective, observational, multicentred study. Arch Dis Child Fetal Neonatal Ed. 2014 Mar 19. doi: 10.1136/archdischild-2013-304747. [Epub ahead of print]
2. Gibson BE, Todd A, Roberts I, Pamphilon D, Rodeck C, Bolton-Maggs P, Burbin G, Duguid J, Boulton F, Cohen H, Smith N, McClelland DB, Rowley M, Turner G; British Commitee for Standards in Haematology Transfusion Task Force: Writing group. Transfusion guidelines for neonates and older children. Br J Haematol. 2004 Feb;124(4):433-53.
3. Neary E, Okafor I, Al-Awaysheh F, et al. Laboratory coagulation parameters in extremely premature infants born earlier than 27 gestational weeks upon admission to a neonatal intensive care unit. Neonatology 2013;104:222-7.
4. Andrew M, Paes B, Milner R, et al. Development of the human coagulation system in the healthy premature infant. Blood 1988;72:1651-7.
Conflict of Interest:
Physiolgical transition ?
We congratulate the authors on this study of neonatal transitional circulation performed so quickly after birth. The authors state that the ductal flow ratio reported in their study reflects pulmonary and haemodynamic transition and can be used to monitor neonatal transition in healthy infants. The implication is that their study describes a physiological transition in healthy term infants, but we question that this is the case.
Delivery by elective caesarean section is not a physiological birth but it does permit the neonate an atraumatic birth. We are particularly concerned that the transition may have been disrupted by the timing of cord clamping which was between 30 and 60 seconds. While this is considered delayed cord clamping by some, most guidelines recommend a minimum of 60 seconds have elapsed before the circulation is interrupted by cord clamping. The WHO advises 3 minutes.(1) Not all of the babies in the series had established respiration before clamping and cord clamping before the onset of respiration has a marked effect on cardiac output.(2) It is therefore questionable that the mean and range of results published represents a normal transition in healthy infants.
The normal fetal circulation is well described with the two ventricles pumping in parallel, the right ventricular output being significantly more than the left and the flow across two shunts, right to left in the ductus arteriousus and right to left across the foramen ovale. The normal neonatal circulation is also well described with equal outputs by both ventricles and closed shunts. A closer look at the results suggest some anomalous flow not readily compatible with the end result of the neonatal circulation. For example at ten minutes the mean right ventricular output is 343 mls/kg/min and mean left ventricular output is 212 mls/kg/min and the DA flow is 8mls/kg/min left to right. (ratio R to L =0.9). Where does the right ventricle get the 343 output as only 212 - 8 are reaching the systemic circulation and returning to the right atrium. Also if the pulmonary blood flow is 343+8 = 351, the excess of 141 must be spilling left to right across the foramen ovale. Reverse flow in the foramen ovale is described but has not been quantified. We question that these flows are evidence that this heart is now close to transitioning to a parallel ventricular pattern with equal outputs. Reverse flow across the foramen ovale of 141 is contributing to over 40% of the right ventricular output. This blood has just been through the pulmonary circulation and is oxygenated but is now returning to the right ventricle to be pumped through the pulmonary circulaton once more. Such flow is completely inefficient. Can the authors explain this anomaly in physiogical terms or could this finding in fact be a demonstration that the early clamping at under 60 seconds sometimes before the onset of respiration has indeed disrupted the transitional circulation ?
Reference 1. World Health Organization (WHO), US Agency for International Development (US AID), Maternal and Child Health Integrated Program (MCHIP). (2013). Delayed cord clamping of the umbilical cord to reduce infant anaemia. Updated 2013. Available from: http://www.mchip.net/node/1562 (Accessed June 12, 2014). 2. Bhatt S, Alison BJ,Wallace EM, Crossley KJ, Gill AW, Kluckow M, et al. Delaying cord clamping until ventilation onset improves cardiovascular function at birth in preterm lambs. J Physiol 2013 591(Pt 8): 2113-26.
Conflict of Interest:
I am a co-inventer of the LifeStart trolley
Re:Cardiac assessment using echocardiography in the sick neonate - An unmet need for a training syllabus for aspiring neonatologists
Dear Editor I would like to thank Dr's Madar and Kariholu for their interest in the recent review article on use of ultrasound to assess the haemodynamic status of the sick neonate(1,2). They raise an important point that highlights the current disconnect between the recognition of the usefulness of ultrasound in general for assessment of sick neonates and the lack of availability of suitable training courses to learn these skills. They further propose that ultrasound is an essential skill for the neonatologist and thus a training syllabus in neonatal functional cardiac assessment should be developed, and foreshadow the incorporation of this training into neonatal training programs. Neonatology is not alone in this realisation and there is a steady push to incorporate ultrasound to help guide clinical care into many specialty training programs ranging from intensive care, accident and emergency to surgery and renal medicine(3). Separation of the use of point of care ultrasound to guide clinical care from a high level consultational ultrasound to exclude structural pathology is key to gaining acceptance for the use of ultrasound in this way. In Neonatology it is important to avoid describing a focused clinical cardiac ultrasound as an echocardiogram, as this is a term that is usually interpreted as meaning a high level cardiology based examination, with different expectations and outcomes. In Australia and New Zealand we have developed a point of care ultrasound training program for both cardiac and cranial ultrasound(4). The course has a basic and an advanced module and is based on the following principles: 1] A physics and safety module 2] An initial introductory theory and hands on course 3] Self directed learning, logbooking and supervision of ultrasound in a clinical neonatal setting 4] Logbook and competency assessment 5] Reaccreditation requirements We have found that learning neonatal ultrasound in this "apprenticeship" setting, similar to that of learning neonatology generally, results in clinicians who have a clear understanding of the uses and limitations of ultrasound use in the NICU. Contrary to concerns raised by traditional users of ultrasound in the neonatal unit, we have found that not only is physiological management of the sick neonate made easier, but that significant structural cardiac defects are often identified earlier in the neonatal course than had been the case before the increased use of ultrasound to guide clinical care. We have not as yet mandated this training as part of the national neonatal training program, mainly because we are unable to guarantee access to training to all trainees. This will change as the critical mass of neonatologists using ultrasound increases. I encourage Dr's Madar and Kariholu to engage with colleagues interested in developing a neonatal ultrasound training program in the United Kingdom and make it a reality.
(1).Kluckow M Use of ultrasound in the haemodynamic asessment of the sick neonate. Arch. Dis. Child. Fetal Neonatal Ed. 2014 99:F332-F337; doi:10.1136/archdischild-2013-304926 (2). John Madar, Ujwal Kariholu. Cardiac assessment using echocardiography in the sick neonate - An unmet need for a training syllabus for aspiring neonatologists.Arch. Dis. Child. Fetal Neonatal Ed. 2014 (3). Moore CL and Copel JA. Point of care ultrasonography. N Engl J Med. 2011 Feb 24;364(8):749-57 (4). http://www.asum.com.au/newsite/Education.php?p=CCPU-Neonatal
Conflict of Interest:
Cardiac assessment using echocardiography in the sick neonate - An unmet need for a training syllabus for aspiring neonatologists
In the UK speciality training through the grid scheme has been in existence for about a decade with a well-defined syllabus of knowledge and skills deemed necessary for the qualified neonatologist. Although much emphasis is laid on various aspects of neonatal care and the acquisition of procedural skills including cranial ultrasound, cardiac assessment using echocardiography is still considered to be an optional skill (1).
There are many reasons why this position should now be challenged. Not least the greatly enhanced armentarium of the neonatologist when considering therapy, coupled to the relative ease of access to the equipment necessary to undertake such an evaluation.
Hence our question 'Should cardiac assessment using echocardiography be considered an essential skill for the neonatologist?'
The recent article by Kluckow (2) highlights the value of clinician performed cardiac ultrasound in neonatal practice. The ability to undertake a timely competent functional cardiac assessment - even of limited parameters - might help optimise therapy, reduce morbidity and potentially mortality. Yet this ability is not yet deemed essential in the training of those looking after the most vulnerable babies.
A syllabus in functional cardiac assessment for the neonatologist needs to be developed as a matter of priority, with access to structured training in order that all those aspiring to be neonatologists learn the potential of these techniques and are able to acquire the skills during their time as a trainee. It might be argued that it would be advantageous for those already working in the field but who lack these abilities to do likewise.
1. http://www.rcpch.ac.uk/training-examinations-professional- development/postgraduate-training/sub-specialty-training/neonatal
2. Kluckow M. Use of ultrasound in the haemodynamic assessment of the sick neonate. Arch Dis Child Fetal Neonatal Ed. 2014 Apr 15. doi: 10.1136/archdischild-2013-30492
Conflict of Interest:
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