Displaying 1-10 letters out of 572 published
Oxygenation is not the only factor regulating heart rates at birth.
The alternative explanation for the cardiovascular differences between immediate and delayed cord clamping at birth suggested in this commentary is not new and has been acknowledged for over 50 years. The basic premise is that asphyxia is the underlying cause of birth-related bradycardias and that avoiding asphyxia will avoid the bradycardia and associated cardiac instability. However, neonatologists have known for almost as long that lung aeration is the primary consideration when resuscitating bradycardic infants at birth. While it was thought that the beneficial effects are due to increased oxygenation, the Bhatt (1) study showed that increasing pulmonary blood flow and restoring venous return lost due to cord clamping, was also a major contributing factor. This is supported by studies in asphyxic, bradycardic lambs (2). Although the association between severe asphyxia and bradycardia is well- established, most birth related bradycardias are unlikely to be caused by asphyxia. Indeed, the birth-related cardiovascular changes are often unrelated to changes in oxygenation, which is shown in the heart rate normograms published by Dawson (3) et al. In normal healthy term infants, over 50% had a heart rate below 100 bpm at 1 min after birth and in some infants, the heart rates increased while oxygenation remained unchanged or decreased. The Bhatt et al (1) study was designed to replicate a relatively common clinical scenario, whereby the elapsed time between delivery, cord clamping and effective ventilation onset is ~2min. As preterm infants are commonly given an opportunity to transition unassisted at birth, a 2 min time window between birth and the onset of effective respiratory support is not uncommon. To put this into context, lambs at this age do not initiate gasping until 4-5 min after cord clamping, can easily be resuscitated after 10 min and take 12-13 min before becoming asystolic (4). In the Bhatt (1) study, lambs did not gasp and heart rates did not decrease below 100 bpm and so they were only mildly asphyxic at worst. As the fetal heart rate (in utero) responses to cord clamping markedly differ from the heart response to cord clamping ex utero (4), making conclusions about neonatal cardiac responses based on fetal data is problematic. Similar problems arise if the newborn's face is surrounded by liquid (4). We note that in the study cited by the author, a saline-filled bag was placed over the lamb's head and the lambs were ventilated via a tracheostomy. Nevertheless, the alternative interpretation of their findings is that reducing the timing between cord clamping and ventilation onset leads to a more labile transition not because of oxygenation differences, but because it reduces the time that venous return and cardiac output are reduced. This is consistent with the conclusion of Bhatt et al (1). We disagree with the author's suggestion that avoiding asphyxia will by itself improve cardiovascular stability at birth. This is not only because of the reasons cited above, but because this simple view of the physiology surrounding transition will encourage clinicians to intervene and attempt to assist infants earlier than is perhaps necessary.
1. Bhatt S, Alison B, Wallace EM, et al. Delaying cord clamping until ventilation onset improves cardiovascular function at birth in preterm lambs. J Physiol. 2013;591:2113-26.
2. Klingenberg C, Sobotka KS, Ong T, et al. Effect of sustained inflation duration; resuscitation of near-term asphyxiated lambs. Arch Dis Child Fetal Neonatal Ed. 2013;98:F222-7.
3. Dawson JA, Kamlin CO, Wong C, et al. Changes in heart rate in the first minutes after birth. Arch Dis Child Fetal Neonatal Ed. 2010;95:F177- 81.
4. Sobotka KS, Morley C, Ong T, et al. Circulatory Responses to Asphyxia Differ if the Asphyxia Occurs In Utero or Ex Utero in Near-Term Lambs. PLoS One. 2014;9:e112264.
Conflict of Interest:
Early cord clamping and stability of the circulatory transition during preterm birth
The review by Hooper et al1 is timely and mounts a compelling case for a stable circulatory transition during preterm birth. However, advocacy of early ventilation with delayed cord clamping as the primary way forward to ensure such a transition is open to question, as the main supportive evidence for this paradigm comes from an experimental study by the same group,2 for which an alternative interpretation of observed findings has recently come to light. Thus, in preterm lambs, Bhatt et al2 reported relatively minor perinatal changes in heart rate, blood pressure and right ventricular output with early ventilation and delayed cord clamping. By contrast, early cord clamping followed by ventilation 2 minutes later was associated with 1) bradycardia, arterial blood pressure swings and large reductions in right ventricular output before ventilation, and 2) substantial rises in heart rate, blood pressure and right ventricular output after ventilation. The 2 minute interval employed by Bhatt et al2 between early cord clamping and the onset of ventilation is potentially problematic, however, as prior studies in fetal lambs have shown that asphyxia can develop within 2 minutes after complete occlusion of uterine arteries or the umbilical cord.3 4 Indeed, a preterm lamb birth study employing a lesser cord clamp- to-ventilation interval (1.5 minutes) has now shown that an asphyxial state rapidly develops by 45 seconds after cord clamping on aortic blood gas analysis, with a haemoglobin O2 saturation of <10% and O2 tension of <10 mmHg, associated with a fall in pH and rise in CO2 tension.5 Furthermore, similar to the onset and offset phases of brief in utero asphyxia,3 4 this asphyxial state was accompanied by 1) bradycardia, marked falls in ventricular outputs/central blood flows and redistribution of systemic flow towards the brain before ventilation, and 2) tachycardia with blood pressure and flow surges after ventilation.5 These data therefore suggest that the findings of Bhatt et al2 primarily reflected the haemodynamic effects of asphyxia occurring with an extended cord clamping-to-ventilation interval, rather than beneficial effects per se of early ventilation with delayed cord clamping. Consistent with the foregoing proposition, reducing the cord clamping-to- ventilation interval from 1.5 to 0.5 minutes (to avoid development of an established asphyxial state) markedly blunted perinatal haemodynamic fluctuations.5 This finding thus implies that circulatory stability during the preterm birth transition hinges on avoidance of asphyxia. Such avoidance can be achieved not only with the advocated paradigm of early ventilation and delayed cord clamping,1 but also with early cord clamping, if this is followed by a short interval before the onset of ventilation.5 References 1. Hooper SB, Polglase GR, te Pas AB. A physiological approach to the timing of umbilical cord clamping at birth. Arch Dis Child Fetal Neonatal Ed 2014; DOI: 10.1136/archdischild-2013-305703. 2. Bhatt S, Alison BJ, Wallace EM, et al. Delaying cord clamping until ventilation onset improves cardiovascular function at birth in preterm lambs. J Physiol 2013;591:2113-26. 3. Jensen A, Garnier Y, Berger R. Dynamics of fetal circulatory responses to hypoxia and asphyxia. Eur J Obstet Gynecol Reprod Biol 1999;84:155-72. 4. Hunter CJ, Blood AB, Power GG. Cerebral metabolism during cord occlusion and hypoxia in the fetal sheep: a novel method of continuous measurement based on heat production. J Physiol 2003;552:241-51. 5. Smolich JJ, Kenna KR, Cheung MM. Onset of asphyxial state in non- respiring interval between cord clamping and ventilation increases hemodynamic lability of birth transition in preterm lambs. J Appl Physiol 2015; DOI: 10.1152/japplphysiol.01147.2014.
Conflict of Interest:
Neonatal airway problems and the can't intubate can't ventilate scenario
To: The Editor, Archives of Disease in Childhood
From: Dr Janet M Rennie Dr Giles S Kendall (NICU UCLH London)
Dr Caroline May (NICU & NTS The Royal London Hospital, London)
Comment on: Neonatal Airway Practices: Whitby T et al ADC Fetal and Neonatal Edition 2015:100: F92-93
We read the letter from Whitby et al regarding neonatal airway practice with interest. We agree that neonatal units need a "difficult airway" trolley, a guideline, and a "Can't Intubate, Can't ventilate" (CICV) algorithm. Like many units, we have thought hard about this over the last year and have reflected on our own clinical experiences.
We suggest that the CICV algorithm proposed by Whitby et al is not suitable for translation to the newborn. There are several reasons why the newborn require a special approach; this is not "inequality". Most importantly, as pointed out by Johansen and colleagues, the cricothyroid space is simply too small to cannulate in a neonate and surgical cricothyrotomy is not an option (Johansen et al., 2012). Very few neonatal units would be able to obtain the services of an experienced paediatric ENT surgeon, or have the equipment for emergency tracheostomy, and this is only feasible in the larger term newborn even then and very few patients are unconscious at the time of acute airway compromise. Storz laryngoscopes (and other indirect laryngoscopes) are fantastic aids but it is impractical for such valuable equipment to form part of a "difficult airway" set kept in storage on a neonatal unit.
We have had good success with the use of a bougie and the "railroad" technique, which is not mentioned at all in the algorithm proposed by Whitby et al. Laryngeal mask airways can certainly help, and the Igel devise looks promising. Further, a neonatal algorithm needs to recognise the possibility of a congenital problem such as Pierre Robin sequence, which requires recognition and special management (Abel et al., 2012) (Evans et al., 2011). Anticipation and planned securing of difficult airways is particularly important where congenital anomalies are known and rather disappointingly there is no mention of such planning in the Whitby algorithm. Such plans often need to be bespoke and carefully considered when facing such unique clinical situations and the baby's clinical condition may in fact be exacerbated by cricothyrotomy/tracheostomy eg. laryngeal web.
In short, we agree that a CICV algorithm and a realistic "difficult airway" kit list are needed, but these need to be appropriate for the newborn and to be achievable by all units.
Abel, F., Bajaj, Y., Wyatt, M. & Wallis, C. (2012). The successful use of the nasopharyngeal airway in Pierre Robin sequence: an 11-year experience. Arch Dis Child 97, 331-4. Evans, K. N., Sie, K. C., Hopper, R. A., Glass, R. P., Hing, A. V. & Cunningham, M. L. (2011). Robin sequence: from diagnosis to development of an effective management plan. Pediatrics 127, 936-48. Johansen, L. C., Mupanemunda, R. H. & Danha, R. F. (2012). Managing the newborn infant with a difficult airway. Infant 8, 116-119.
Conflict of Interest:
UNICEF Baby Friendly Initiative and Vitamin D
Cleminson and co-authors are to be commended for their excellent and comprehensive work, which raises awareness to an important health issue(1). Breastfeeding has undoubted benefits. However, it is important to recognise, when promoting the health benefits, of breastfeeding that breastmilk has very low levels of vitamin D (20IU or 0.5micrograms/litre)(2,3). This places infants, who are exclusively breastfed, at risk of vitamin D deficiency and even rickets. The World Health Organisation (WHO) recommends that infants be exclusively breastfed in their first six months. However this would not satisfy a child's daily vitamin D requirements. Such an infant would receive less than a tenth of the daily 8.5micrograms recommended by the Department of Health (DoH) for infants aged 0-6months(3); and required for normal growth(4).
The majority of vitamin D originates from dermal photosynthesis, in Europe and the USA (5). At latitudes greater than 33 degrees North, there is insufficient sunlight to generate adequate vitamin D in the winter months. In Edmonton, Canada (52 degrees North) and Newcastle, UK (54 degrees North); vitamin D dermal photosynthesis is not possible for six months of the year(6). The magnitude of the problem cannot be overstated. Hospitalisation for rickets, for those under 15 years, has increased five- fold in the UK between 1990 and 2011(7). According to the UK National Diet and Nutrition Survey, 25% of the UK population are vitamin D deficient (25 -hydroxyvitamin D<25nmol/l)(8).
The DoH 2012, NICE 2008/2014 and Scientific Advisory Committee on Nutrition 2007 guidance recommend that all pregnant and lactating mothers receive a daily supplement containing 10micrograms of vitamin D (8,9,10,11). They also advocate that all children from 6 months to 5years receive vitamin D supplements. However, vitamin D supplementation is indicated from birth for infants, if the mother did not receive vitamin D supplements during pregnancy or if they belong to at-risk groups. This includes those with dark skin types and/or with little sunlight exposure.
UNICEF explicitly supports this NICE guidance within the Baby Friendly Initiative(12). The US Centre for Disease Control (CDC), for their part, recommend 400IU daily vitamin D supplementation for all breastfed infants, from birth(13,14). UNICEF, NICE, DoH and CDC emphasise the importance of educating mothers and healthcare professionals on the vital role of supplementary vitamin D for mothers and infants during lactation. This important message must be promulgated along with the health benefits of breastfeeding.
1. Cleminson J, Oddie S, Renfrew MJ, McGuire W. Being baby friendly: evidence-based breastfeeding support. Arch Dis Child Fetal Neonatal Ed. 2014 Oct 7. pii: fetalneonatal-2013-304873. doi: 10.1136/archdischild-2013 -304873.
2. Vitamin D deficiency Holick NEJM 2007; 357:266-81
3. Elder CJ, Bishop NJ. Rickets. Lancet. 2014; 383:1665-7
4. Jeans PC, Stearns G. Effectiveness of vitamin D in infancy in relation to the vitamin source. Proc Soc Exp Biol Med 1934; 31:1159-61
5. Braegger C, Campoy C, Colomb V, Decsi T, Domellof M, Fewtrell M, Hojsak I, Mihatsch W, Molgaard C, Shamir R, Turck D, van Goudoever J; on Behalf of the ESPGHAN Committee on Nutrition.Vitamin D in the Healthy European Paediatric Population. J Pediatr Gastroenterol Nutr. 2013;56:692-
6. Wacker M, Holick MF. Sunlight and Vitamin D: A global perspective for health. Dermatoendocrinol. 2013; 5:51-108
7. Goldacre M, Hall N, Yeates DG. Hospitalisation for children with rickets in England: a historical perspective. Lancet. 2014; 383: 597- 8
10. http://www.nice.org.uk/guidance/ph11/resources/guidance- maternal-
11. http://www.nice.org.uk/guidance/gid- phg71/documents/implementing-
Conflict of Interest:
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:
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