Thank you for an interesting case but the position of the arterial catheter after the perforation suggests to me that this was from an umbilical artery rather than the aorta (compare the path on the abdominal wall on the 2 x-rays).
This may therefore be why you were able to successfully manage this conservatively.
We kindly thank Da Lozzo et al. for their reaction to our paper. Indeed, many variables may be of influence on the incidence of thrombosis in our study group.
The authors are correct that the incidence of necrotizing enterocolitis in our study group (12.5%, 5/40) is higher than expected based on literature. As shown by Battersby et al. comparing NEC incidences internationally is challenging (1). The incidence of NEC in our study group does not reflect the NEC incidence of last 15 years at our department (which was 3.7% (98/2626) in infants with a gestational age <32 weeks). Possibly, the higher incidence of NEC led to a higher incidence of thrombosis in our study. However, care should be taken when interpreting our results due to the small sample size (n=40).
Da Lozzo et al. make a valuable point about the diameter of central venous catheters. Most (25/40) umbilical venous catheters (UVCs) used in our study-group were 4Fr Vygon catheters, single or double lumen, with an external diameter of 1.5 and 1.4 mm, respectively (strange enough double lumen is smaller than single lumen). In 3/40 infants 5Fr Vygon catheters (external diameter 1.7 mm) were used and in 10/40 infants 3.5Fr Vygon catheters (external diameter 1.16 mm). In 2/40 infants the size of the catheter was not registered. We found no association between the risk of thrombosis and the size of the catheter (p=0.59). However, as stated in the discussion of our paper, the sample size of our group is too...
We kindly thank Da Lozzo et al. for their reaction to our paper. Indeed, many variables may be of influence on the incidence of thrombosis in our study group.
The authors are correct that the incidence of necrotizing enterocolitis in our study group (12.5%, 5/40) is higher than expected based on literature. As shown by Battersby et al. comparing NEC incidences internationally is challenging (1). The incidence of NEC in our study group does not reflect the NEC incidence of last 15 years at our department (which was 3.7% (98/2626) in infants with a gestational age <32 weeks). Possibly, the higher incidence of NEC led to a higher incidence of thrombosis in our study. However, care should be taken when interpreting our results due to the small sample size (n=40).
Da Lozzo et al. make a valuable point about the diameter of central venous catheters. Most (25/40) umbilical venous catheters (UVCs) used in our study-group were 4Fr Vygon catheters, single or double lumen, with an external diameter of 1.5 and 1.4 mm, respectively (strange enough double lumen is smaller than single lumen). In 3/40 infants 5Fr Vygon catheters (external diameter 1.7 mm) were used and in 10/40 infants 3.5Fr Vygon catheters (external diameter 1.16 mm). In 2/40 infants the size of the catheter was not registered. We found no association between the risk of thrombosis and the size of the catheter (p=0.59). However, as stated in the discussion of our paper, the sample size of our group is too small to confirm the influence of risk factors, such as catheter size. As suggested by Barone et al. (2), the external diameter of the catheter should not exceed 1/3 of the internal diameter of the vein to reduce the risk of thrombosis. Since the most frequently used catheter in our study was a double-lumen 4Fr catheter, these catheters would preferably have to be placed in veins with an internal diameter of least 4.2 mm to reduce the risk of thrombosis. Unfortunately, Barone et al. (2) did not report diameters of veins in the umbilical venous catheter route, nor did we measurements of these diameters in our study. Eifinger et al. (3) analyzed the diameter of the umbilical vein and its further course with use of spiral-CT examinations on stillborns. They report an umbilical vein diameter increasing from 3.4 to 11 mm, a ductus venosus diameter of 2.5 mm and an umbilical recess diameter of 5 mm and conclude the umbilical vein and its extensions are wide enough to admit a 4Fr catheter. However, diameters of veins in stillborns, without flow, may not be the same as in living children.
Ultrasonography is nowadays increasingly being used in various NICUs, including our department, to evaluate the position of UVCs during and after insertion. We agree with Da Lozzo et al. that it may be beneficial to use ultrasonography before catheterization to check the internal diameter of the venous route in order to choose the most appropriate sized catheter.
(1) Battersby C, Santhalingam T, Costeloe K, Modi N. Incidence of neonatal necrotising enterocolitis in high-income countries: a systematic review. Arch Dis Child Fetal Neonatal Ed 2018;103(2):F182-F189.
(2) Barone G, D’Andrea V, Vento G, Pittiruti M: A Systematic Ultrasound Evaluation of the Diameter of Deep Veins in the Newborn: Results and Implications for Clinical Practice. Neonatology 2019;115:335-340.
(3) Eifinger F, Fuchs Z, Koerber F, Persigehl T, Scaal M. Investigation of umbilical venous vessels anatomy and diameters as a guideline for catheter placement in newborns. Clin Anat 2018;31(2):269-274.
We appreciated the paper by Dubbink-Verheij et al. evaluating the incidence of thrombosis in newborns who underwent umbilical catheterization in comparison with a control group of infants without umbilical venous catheter (UVC). While the paper highlights specific issues about UVC-related thrombosis in NICU, regarding the sites, the time of onset and the outcomes of this condition, we suggest that some relevant variables have not been taken fully in account.
Some of the comorbidity rates of the patients in the study group are not consistent with data from literature and might have had a role in the unusual high rate of thrombosis and poor outcome in the study group. The reported rates of necrotizing enterocolitis (NEC; 12.5% in the study group, 10% in the total population of the study) is significantly higher compared with that of the Vermont Oxford Network (VON); VLBW infants between 2000 and 2009 based on the VON showed a NEC incidence of 4.6-6.1%. (1)
The study reported 30 thrombotic episodes in defined locations but, remarkably, the type and the diameter of catheter utilized was not stated by the Authors. Neonates, and especially preterm neonates, have an unfavorable catheter-to-vessel diameter ratio, which is a recognized risk factor for the development of catheter-related thrombosis in CVCs. In a in vitro model Nifong and McDevitt (2) quantified the impact of the catheter to vein size ratio on fluid flow unraveling the mechanism by which risk of catheter-...
We appreciated the paper by Dubbink-Verheij et al. evaluating the incidence of thrombosis in newborns who underwent umbilical catheterization in comparison with a control group of infants without umbilical venous catheter (UVC). While the paper highlights specific issues about UVC-related thrombosis in NICU, regarding the sites, the time of onset and the outcomes of this condition, we suggest that some relevant variables have not been taken fully in account.
Some of the comorbidity rates of the patients in the study group are not consistent with data from literature and might have had a role in the unusual high rate of thrombosis and poor outcome in the study group. The reported rates of necrotizing enterocolitis (NEC; 12.5% in the study group, 10% in the total population of the study) is significantly higher compared with that of the Vermont Oxford Network (VON); VLBW infants between 2000 and 2009 based on the VON showed a NEC incidence of 4.6-6.1%. (1)
The study reported 30 thrombotic episodes in defined locations but, remarkably, the type and the diameter of catheter utilized was not stated by the Authors. Neonates, and especially preterm neonates, have an unfavorable catheter-to-vessel diameter ratio, which is a recognized risk factor for the development of catheter-related thrombosis in CVCs. In a in vitro model Nifong and McDevitt (2) quantified the impact of the catheter to vein size ratio on fluid flow unraveling the mechanism by which risk of catheter-related thrombosis increases with the size of the catheter. On that basis, in 2009 Barone et al. (3) performed a systematic ultrasound evaluation of the diameter of deep veins in newborns, suggesting that the external diameter of the catheter should not exceed 1/3 of the internal diameter of the vein to reduce the risk of thrombosis. According to these evidences, we believe that catheter caliber is a relevant variable that should be reported in studies aiming to assess the risk of CVCs-related thrombosis.
(1) Jeffrey D. Horbar, et al. Mortality and Neonatal Morbidity Among Infants 501 to 1500 Grams From 2000 to 2009, Pediatrics Jun 2012; 129; 1019
(2) Nifong TP, McDevitt TJ. The effect of catheter to vein ratio on blood flow rates in a simulated model of peripherally inserted central venous catheters. Chest. 2011 Jul; 140(1): 48–53.
(3) Barone G, D’Andrea V, Vento G, Pittiruti M: A Systematic Ultrasound Evaluation of the Diameter of Deep Veins in the Newborn: Results and Implications for Clinical Practice. Neonatology 2019;115:335-340.
Prisca Da Lozzo MD. Cristina Bibalo MD. Francesca Galdo MD. Francesco Maria Risso MD. Neonatal Intensive Care Unit, Institute for Child Health IRCCS Burlo Garofolo, Trieste, Italy.
I read with interest this review by Dr Padidela et al.
I would like the authors to comment on the following issues:
1. The review is suggesting significant change to current UK practice but does not review any data to suggest that current practice is causing secondary hyperparathyroidism ( apart from an anecdotal case discussed). While the recommendations may have merit based on physiology , it seems suboptimal to recommend a significant change of practice without any data to clearly show that current practice is causing a problem.
2. The review recommends measurement of plasma parathromone as a critical initial step and most of the subsequent practice is dictated by this. The authors state " measurement of plasma PTH both for screening and diagnosis is crucially important". In the very next line they however state "the reference range of plasma PTH in neonates is not well established" They then go to talk about a very small study of 20 preterm neonates.
It does not make much sense to recommend a major change of practice without any data to back it up and then highlight plasma PTH as a critical investigation for decision making when we don't really have any robust normative data.
Should we not instead be generating prospective data based on current practice and if there is evidence of secondary hyperparathyroidism to change treatment accordingly? Also should we not be generating normative data for various gestati...
I read with interest this review by Dr Padidela et al.
I would like the authors to comment on the following issues:
1. The review is suggesting significant change to current UK practice but does not review any data to suggest that current practice is causing secondary hyperparathyroidism ( apart from an anecdotal case discussed). While the recommendations may have merit based on physiology , it seems suboptimal to recommend a significant change of practice without any data to clearly show that current practice is causing a problem.
2. The review recommends measurement of plasma parathromone as a critical initial step and most of the subsequent practice is dictated by this. The authors state " measurement of plasma PTH both for screening and diagnosis is crucially important". In the very next line they however state "the reference range of plasma PTH in neonates is not well established" They then go to talk about a very small study of 20 preterm neonates.
It does not make much sense to recommend a major change of practice without any data to back it up and then highlight plasma PTH as a critical investigation for decision making when we don't really have any robust normative data.
Should we not instead be generating prospective data based on current practice and if there is evidence of secondary hyperparathyroidism to change treatment accordingly? Also should we not be generating normative data for various gestations and postnatal ages to be confident about the plasma PTH values?
3. In figure 1, the first part shows a right humerus at 3 months of age but the subsequent picture at 5 months which supposedly is to demonstrate healing following vitamin D and calcium therapy is of the left arm. Before and after pics ideally need to be same side and similar resolution to clearly demonstrate the change.
4. We don’t know what proportion of such preterms have secondary hyperparathyroidism and the case discussed in your paper may be a small minority. Rather than advising a significant change of practice would it not be more appropriate to actually prove presence or absence of sec hyperparathyroidism in a larger dataset and develop normative values for PTH for various gestations/postnatal age ranges etc?
We have read with great interest the article by Goel et al and found it very relevant. We have also been following keenly the reports from other units on successful implementation of the KP sepsis calculator in UK. Encouraged by the positive outcomes and increased use of the KP screening tool, 3 tertiary neonatal units in the NW,namely East Lancashire Hospital NHS Trust, Royal Bolton Hospital and Royal Preston Hospital decided to collect 3 months of prospective data of EONS screening and compare its recommendations against the existing practice based on CG149. All of the aforementioned units use specific CRP cut-offs to label and treat as presumed sepsis. Between the 3 units 313 babies were screened for EONS in the 3 months at a screening rate of 8.2%. Although the KP tool would have reduced screening by a significant 72.5% in average, the combined sensitivity and specificity were 50% and 82% respectively. The KP identified all true "blood-culture positive" sepsis but a large number of babies whom the KP would not have recommended screening or observation mounted high CRP responses and ended up getting treated with antibiotics. Now none of these babies were clinically unwell or grew positive blood or CSF cultures. Hence it will be interesting to see whether maternal factors like fever or pre-eclampsia resulted in this high CRP response. It also reflects the lack of accuracy of CRP and flaw in CRP based approach. It is also worth considering whether baseline di...
We have read with great interest the article by Goel et al and found it very relevant. We have also been following keenly the reports from other units on successful implementation of the KP sepsis calculator in UK. Encouraged by the positive outcomes and increased use of the KP screening tool, 3 tertiary neonatal units in the NW,namely East Lancashire Hospital NHS Trust, Royal Bolton Hospital and Royal Preston Hospital decided to collect 3 months of prospective data of EONS screening and compare its recommendations against the existing practice based on CG149. All of the aforementioned units use specific CRP cut-offs to label and treat as presumed sepsis. Between the 3 units 313 babies were screened for EONS in the 3 months at a screening rate of 8.2%. Although the KP tool would have reduced screening by a significant 72.5% in average, the combined sensitivity and specificity were 50% and 82% respectively. The KP identified all true "blood-culture positive" sepsis but a large number of babies whom the KP would not have recommended screening or observation mounted high CRP responses and ended up getting treated with antibiotics. Now none of these babies were clinically unwell or grew positive blood or CSF cultures. Hence it will be interesting to see whether maternal factors like fever or pre-eclampsia resulted in this high CRP response. It also reflects the lack of accuracy of CRP and flaw in CRP based approach. It is also worth considering whether baseline differences in maternal sepsis rates among geographical areas have an impact of the sensitivity of the calculator. It will be helpful and interesting to know whether the authors of this study and also previously reported ones (1) had similar experience with CRP and how they addressed the issue.
Reference :
1. Davidson SL, KIng R, et al. The Kaiser-Permanente early onset sepsis calculator – a tool to reduce antibiotic use in the UK? Neonatal Society summer meeting 2016.
I was interested to read this study looking at a question which is extremely important to mothers of preterm infants who need to exclusively express - "how frequently do I need to express?".
The conclusion that there is no difference in average yield of mothers expressing 5, 6, 7, 8, and 9 times a day will be very useful to mothers who are similar to those included in the study - that is mothers of preterm babies aged at least 10 days (but mostly 15-20 days old), who have good daily expressed milk yield (average yield clustered around 750ml/day for these expressing frequencies). Therefore mothers in this group may feel more confident in reducing their expressing sessions down to a more manageable 5 or 6 per day, which reduces their burden of expressing.
However it could be harmful to extrapolate outside of these characteristics, for example mothers attempting to establish their supply in the first 2 weeks of life. We know that this period may be a critical window to establish milk supply and this study cannot comment on the relationship of early expressing frequency to the establishment of adequate yield (which, to complicate matters further, is poorly defined in the context of prematurity, with a range of daily volume targets from 500-900ml suggested in the literature and by the Unicef Baby Friendly Initiative). Already I have seen the article summarised as "mothers of preterm infants should express milk at least 5 times a day" on social...
I was interested to read this study looking at a question which is extremely important to mothers of preterm infants who need to exclusively express - "how frequently do I need to express?".
The conclusion that there is no difference in average yield of mothers expressing 5, 6, 7, 8, and 9 times a day will be very useful to mothers who are similar to those included in the study - that is mothers of preterm babies aged at least 10 days (but mostly 15-20 days old), who have good daily expressed milk yield (average yield clustered around 750ml/day for these expressing frequencies). Therefore mothers in this group may feel more confident in reducing their expressing sessions down to a more manageable 5 or 6 per day, which reduces their burden of expressing.
However it could be harmful to extrapolate outside of these characteristics, for example mothers attempting to establish their supply in the first 2 weeks of life. We know that this period may be a critical window to establish milk supply and this study cannot comment on the relationship of early expressing frequency to the establishment of adequate yield (which, to complicate matters further, is poorly defined in the context of prematurity, with a range of daily volume targets from 500-900ml suggested in the literature and by the Unicef Baby Friendly Initiative). Already I have seen the article summarised as "mothers of preterm infants should express milk at least 5 times a day" on social media.
Overall this is a useful addition to the literature, but it will be important to ensure that the conclusions are not over-interpreted in clinical practice
Thank you for this interesting article, which really adds to our understanding of management of neonatal hypoglycaemia. However, your conclusion that a subset of babies should receive formula rather than breastfeed alongside gel, depending on their blood glucose level, is not supported by the evidence you have provided and ignores the potential harm associated with this approach.
Your data states that alongside the first use of gel, breastfed babies are more likely to require a second gel. There is no literature to support the idea that experiencing a second transient hypoglycaemia in a carefully monitored baby in the first 48 hours of life is harmful (indeed UK guidance uses a treatment threshold of 2mmol/l for the entire first 48 hours of life), and alongside the second gel breastfeeding is as effective as formula so there is no reason to suppose from the data provided that breastfed babies are more likely to go on to require intravenous dextrose.
Asking breastfeeding mothers to use formula instead of breastfeeding in the first hours of their baby's life is likely to undermine mothers' trust in breastfeeding, may impact on their milk supply through reduced stimulation in the critical time period and reduces the colostrum volume ingested, with its unique immune properties. It is not a recommendation to be made lightly.
As authors of the 2015 guidelines we read with interest the “UK neonatal resuscitation survey” [1]. Comparison with 2012 shows a rewarding positive effect of successive guidelines on newborn resuscitation practice.
However, we wanted to address this statement: “…updated guidelines have been criticised for failing to consider data from the Targeted Oxygen in the Resuscitation of Preterm Infants [To2rpido]”. To2rpido [2], published 2017, was unavailable for inclusion in 2015 ILCOR reviews of evidence. [3]. The analysis referred to was post-hoc and unprespecified. Clinicians were not blinded and recruitment was problematic. Enrolling only 5% of eligible infants, To2rpido was terminated after reaching 15% of targeted sample size due to loss of equipoise: ironically, clinicians were concerned about using high oxygen concentrations.
Nonetheless, To2rpido generated such interest that it led to the first neonatal review in ILCOR’s continuous evidence evaluation strategy. [4] Utilising GRADE methodology to rate quality of evidence and strength of recommendations, To2rpido’s impact was downgraded because of high risk of bias. This review [4] continues to recommend “starting with a lower oxygen concentration (21–30%) compared to higher oxygen concentration (60–100%)” whilst highlighting many gaps in our current knowledge.
The use of end-tidal CO2 (ETCO2) detection was not recommended because the guidelines, and Newborn Life Support (NLS) course, focus on airwa...
As authors of the 2015 guidelines we read with interest the “UK neonatal resuscitation survey” [1]. Comparison with 2012 shows a rewarding positive effect of successive guidelines on newborn resuscitation practice.
However, we wanted to address this statement: “…updated guidelines have been criticised for failing to consider data from the Targeted Oxygen in the Resuscitation of Preterm Infants [To2rpido]”. To2rpido [2], published 2017, was unavailable for inclusion in 2015 ILCOR reviews of evidence. [3]. The analysis referred to was post-hoc and unprespecified. Clinicians were not blinded and recruitment was problematic. Enrolling only 5% of eligible infants, To2rpido was terminated after reaching 15% of targeted sample size due to loss of equipoise: ironically, clinicians were concerned about using high oxygen concentrations.
Nonetheless, To2rpido generated such interest that it led to the first neonatal review in ILCOR’s continuous evidence evaluation strategy. [4] Utilising GRADE methodology to rate quality of evidence and strength of recommendations, To2rpido’s impact was downgraded because of high risk of bias. This review [4] continues to recommend “starting with a lower oxygen concentration (21–30%) compared to higher oxygen concentration (60–100%)” whilst highlighting many gaps in our current knowledge.
The use of end-tidal CO2 (ETCO2) detection was not recommended because the guidelines, and Newborn Life Support (NLS) course, focus on airway management without need for intubation. Both explain how, and when, ETCO2 might be used highlighting limitations to its use. The European guidelines, on which UK guidelines are based, state “detection of exhaled carbon dioxide in addition to clinical assessment is recommended as the most reliable method to confirm tracheal placement in neonates with spontaneous circulation”. [5] Given this, considered and careful use of ETCO2 detection best sits within the Advanced Resuscitation of the Newborn Infant (ARNI) course which teaches care, including intubation, beyond Newborn Life Support.
References:
1. Charles E, Hunt K, Murthy V, Harris C, Greenough A. UK neonatal resuscitation survey. Arch Dis Child Fetal Neonatal Ed 2019;104:F324–F325
2. Oei JL, Saugstad OD, Lui K, Wright IM, Smyth JP, Craven P, Wang YA, McMullan R, Coates E, Ward M, Mishra P, De Waal K, Travadi J, See KC, Cheah IG, Lim CT, Choo YM, Kamar AA, Cheah FC, Masoud A, Tarnow-Mordi W. Targeted Oxygen in the Resuscitation of Preterm Infants, a Randomized Clinical Trial. Pediatrics 2017;139:e20161452.
3. Wyllie J, Perlman JM, Kattwinkel J, Wyckoff MH, Aziz K, Guinsburg R, Kim HS, Liley HG, Mildenhall L, Simon WM, Szyld E, Tamura M, Velaphi S; Neonatal Resuscitation Chapter Collaborators. Part 7: Neonatal resuscitation: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Resuscitation 2015;95:e169–201.
4. Welsford M, Nishiyama C, Shortt C, Weiner G, Roehr CC, Isayama T, Dawson JA, Wyckoff MH, Rabi Y; International Liaison Committee on Resuscitation Neonatal Life Support Task Force. Initial Oxygen Use for Preterm Newborn Resuscitation: A Systematic Review With Meta-analysis. Pediatrics 2019;143:e20181828.
5. Wyllie J, Bruinenberg J, Roehr CC, Rüdiger M, Trevisanuto D, Urlesberger B. European Resuscitation Council Guidelines for Resuscitation 2015: Section 7. Resuscitation and support of transition of babies at birth. Resuscitation 2015;95:249–63.
Dear Editor,
We read with great interest the network meta-analysis performed by Zeng et al [1]. The authors investigated the comparative efficacy and safety of different corticosteroids in the prevention of bronchopulmonary dysplasia in preterm infants. They included 47 RCTs with 6747 participants. We have several concerns about the study.
First, it looks that the authors are unfamiliar with the procedures of network meta-analysis because there were obvious mistakes. Figure 1 in the study was network plot of different corticosteroids. In Figure 1, the circle size should be proportional to the sample size randomised to each intervention [2]. The line width should be proportional to the study numbers of each direct comparison. However, the circle size was not proportional to the sample size in Figure 1. The line width between dexamethasone (high dose) and placebo also seems inadequate.
Second, various statistical methods or plots have been suggested to assist interpreting the results of network meta-analysis [3]. However, many of them were not performed or presented in this study. For example, since there were direct estimates (i.e., results of pairwise meta-analysis) and indirect estimates (i.e., results of network meta-analysis), the inconsistency between them should be assessed and explored because important inconsistency could threaten the validity of the results. Besides, the authors also didn’t assess small-study effects. Small-study effects could mat...
Dear Editor,
We read with great interest the network meta-analysis performed by Zeng et al [1]. The authors investigated the comparative efficacy and safety of different corticosteroids in the prevention of bronchopulmonary dysplasia in preterm infants. They included 47 RCTs with 6747 participants. We have several concerns about the study.
First, it looks that the authors are unfamiliar with the procedures of network meta-analysis because there were obvious mistakes. Figure 1 in the study was network plot of different corticosteroids. In Figure 1, the circle size should be proportional to the sample size randomised to each intervention [2]. The line width should be proportional to the study numbers of each direct comparison. However, the circle size was not proportional to the sample size in Figure 1. The line width between dexamethasone (high dose) and placebo also seems inadequate.
Second, various statistical methods or plots have been suggested to assist interpreting the results of network meta-analysis [3]. However, many of them were not performed or presented in this study. For example, since there were direct estimates (i.e., results of pairwise meta-analysis) and indirect estimates (i.e., results of network meta-analysis), the inconsistency between them should be assessed and explored because important inconsistency could threaten the validity of the results. Besides, the authors also didn’t assess small-study effects. Small-study effects could materially alter the relative effectiveness and ranking of treatments. The ‘comparison-adjusted’ funnel plot has been suggested to assess the presence of small-study effects. Model that adjusted for small-study effects should be performed if small-study effects was found.
References
1. Zeng L, Tian J, Song F, et al. Corticosteroids for the prevention of bronchopulmonary dysplasia in preterm infants: a networkmeta-analysis. Arch Dis Child Fetal Neonatal Ed. 2018 Nov;103(6):F506-F511.
2. Dias S, Caldwell DM. Network meta-analysis explained. Arch Dis Child Fetal Neonatal Ed. 2019 Jan;104(1):F8-F12.
3. Chaimani A, Higgins JP, Mavridis D, Spyridonos P, Salanti G. Graphical tools for network meta-analysis in STATA. PLoS One. 2013 Oct 3;8(10):e76654.
There seems to be a descrepency regarding the number of babies intubatec in two groups. 56 babies were intubated in high tidal volume group against 14 intubated in the low tidal volume group as per the article. I wondering whether it might have contributed to the high incidence of IVH in the high tidal volume group.
Thank you for an interesting case but the position of the arterial catheter after the perforation suggests to me that this was from an umbilical artery rather than the aorta (compare the path on the abdominal wall on the 2 x-rays).
This may therefore be why you were able to successfully manage this conservatively.
We kindly thank Da Lozzo et al. for their reaction to our paper. Indeed, many variables may be of influence on the incidence of thrombosis in our study group.
Show MoreThe authors are correct that the incidence of necrotizing enterocolitis in our study group (12.5%, 5/40) is higher than expected based on literature. As shown by Battersby et al. comparing NEC incidences internationally is challenging (1). The incidence of NEC in our study group does not reflect the NEC incidence of last 15 years at our department (which was 3.7% (98/2626) in infants with a gestational age <32 weeks). Possibly, the higher incidence of NEC led to a higher incidence of thrombosis in our study. However, care should be taken when interpreting our results due to the small sample size (n=40).
Da Lozzo et al. make a valuable point about the diameter of central venous catheters. Most (25/40) umbilical venous catheters (UVCs) used in our study-group were 4Fr Vygon catheters, single or double lumen, with an external diameter of 1.5 and 1.4 mm, respectively (strange enough double lumen is smaller than single lumen). In 3/40 infants 5Fr Vygon catheters (external diameter 1.7 mm) were used and in 10/40 infants 3.5Fr Vygon catheters (external diameter 1.16 mm). In 2/40 infants the size of the catheter was not registered. We found no association between the risk of thrombosis and the size of the catheter (p=0.59). However, as stated in the discussion of our paper, the sample size of our group is too...
We appreciated the paper by Dubbink-Verheij et al. evaluating the incidence of thrombosis in newborns who underwent umbilical catheterization in comparison with a control group of infants without umbilical venous catheter (UVC). While the paper highlights specific issues about UVC-related thrombosis in NICU, regarding the sites, the time of onset and the outcomes of this condition, we suggest that some relevant variables have not been taken fully in account.
Show MoreSome of the comorbidity rates of the patients in the study group are not consistent with data from literature and might have had a role in the unusual high rate of thrombosis and poor outcome in the study group. The reported rates of necrotizing enterocolitis (NEC; 12.5% in the study group, 10% in the total population of the study) is significantly higher compared with that of the Vermont Oxford Network (VON); VLBW infants between 2000 and 2009 based on the VON showed a NEC incidence of 4.6-6.1%. (1)
The study reported 30 thrombotic episodes in defined locations but, remarkably, the type and the diameter of catheter utilized was not stated by the Authors. Neonates, and especially preterm neonates, have an unfavorable catheter-to-vessel diameter ratio, which is a recognized risk factor for the development of catheter-related thrombosis in CVCs. In a in vitro model Nifong and McDevitt (2) quantified the impact of the catheter to vein size ratio on fluid flow unraveling the mechanism by which risk of catheter-...
I read with interest this review by Dr Padidela et al.
I would like the authors to comment on the following issues:
1. The review is suggesting significant change to current UK practice but does not review any data to suggest that current practice is causing secondary hyperparathyroidism ( apart from an anecdotal case discussed). While the recommendations may have merit based on physiology , it seems suboptimal to recommend a significant change of practice without any data to clearly show that current practice is causing a problem.
2. The review recommends measurement of plasma parathromone as a critical initial step and most of the subsequent practice is dictated by this. The authors state " measurement of plasma PTH both for screening and diagnosis is crucially important". In the very next line they however state "the reference range of plasma PTH in neonates is not well established" They then go to talk about a very small study of 20 preterm neonates.
Show MoreIt does not make much sense to recommend a major change of practice without any data to back it up and then highlight plasma PTH as a critical investigation for decision making when we don't really have any robust normative data.
Should we not instead be generating prospective data based on current practice and if there is evidence of secondary hyperparathyroidism to change treatment accordingly? Also should we not be generating normative data for various gestati...
We have read with great interest the article by Goel et al and found it very relevant. We have also been following keenly the reports from other units on successful implementation of the KP sepsis calculator in UK. Encouraged by the positive outcomes and increased use of the KP screening tool, 3 tertiary neonatal units in the NW,namely East Lancashire Hospital NHS Trust, Royal Bolton Hospital and Royal Preston Hospital decided to collect 3 months of prospective data of EONS screening and compare its recommendations against the existing practice based on CG149. All of the aforementioned units use specific CRP cut-offs to label and treat as presumed sepsis. Between the 3 units 313 babies were screened for EONS in the 3 months at a screening rate of 8.2%. Although the KP tool would have reduced screening by a significant 72.5% in average, the combined sensitivity and specificity were 50% and 82% respectively. The KP identified all true "blood-culture positive" sepsis but a large number of babies whom the KP would not have recommended screening or observation mounted high CRP responses and ended up getting treated with antibiotics. Now none of these babies were clinically unwell or grew positive blood or CSF cultures. Hence it will be interesting to see whether maternal factors like fever or pre-eclampsia resulted in this high CRP response. It also reflects the lack of accuracy of CRP and flaw in CRP based approach. It is also worth considering whether baseline di...
Show MoreI was interested to read this study looking at a question which is extremely important to mothers of preterm infants who need to exclusively express - "how frequently do I need to express?".
The conclusion that there is no difference in average yield of mothers expressing 5, 6, 7, 8, and 9 times a day will be very useful to mothers who are similar to those included in the study - that is mothers of preterm babies aged at least 10 days (but mostly 15-20 days old), who have good daily expressed milk yield (average yield clustered around 750ml/day for these expressing frequencies). Therefore mothers in this group may feel more confident in reducing their expressing sessions down to a more manageable 5 or 6 per day, which reduces their burden of expressing.
However it could be harmful to extrapolate outside of these characteristics, for example mothers attempting to establish their supply in the first 2 weeks of life. We know that this period may be a critical window to establish milk supply and this study cannot comment on the relationship of early expressing frequency to the establishment of adequate yield (which, to complicate matters further, is poorly defined in the context of prematurity, with a range of daily volume targets from 500-900ml suggested in the literature and by the Unicef Baby Friendly Initiative). Already I have seen the article summarised as "mothers of preterm infants should express milk at least 5 times a day" on social...
Show MoreThank you for this interesting article, which really adds to our understanding of management of neonatal hypoglycaemia. However, your conclusion that a subset of babies should receive formula rather than breastfeed alongside gel, depending on their blood glucose level, is not supported by the evidence you have provided and ignores the potential harm associated with this approach.
Your data states that alongside the first use of gel, breastfed babies are more likely to require a second gel. There is no literature to support the idea that experiencing a second transient hypoglycaemia in a carefully monitored baby in the first 48 hours of life is harmful (indeed UK guidance uses a treatment threshold of 2mmol/l for the entire first 48 hours of life), and alongside the second gel breastfeeding is as effective as formula so there is no reason to suppose from the data provided that breastfed babies are more likely to go on to require intravenous dextrose.
Asking breastfeeding mothers to use formula instead of breastfeeding in the first hours of their baby's life is likely to undermine mothers' trust in breastfeeding, may impact on their milk supply through reduced stimulation in the critical time period and reduces the colostrum volume ingested, with its unique immune properties. It is not a recommendation to be made lightly.
As authors of the 2015 guidelines we read with interest the “UK neonatal resuscitation survey” [1]. Comparison with 2012 shows a rewarding positive effect of successive guidelines on newborn resuscitation practice.
However, we wanted to address this statement: “…updated guidelines have been criticised for failing to consider data from the Targeted Oxygen in the Resuscitation of Preterm Infants [To2rpido]”. To2rpido [2], published 2017, was unavailable for inclusion in 2015 ILCOR reviews of evidence. [3]. The analysis referred to was post-hoc and unprespecified. Clinicians were not blinded and recruitment was problematic. Enrolling only 5% of eligible infants, To2rpido was terminated after reaching 15% of targeted sample size due to loss of equipoise: ironically, clinicians were concerned about using high oxygen concentrations.
Nonetheless, To2rpido generated such interest that it led to the first neonatal review in ILCOR’s continuous evidence evaluation strategy. [4] Utilising GRADE methodology to rate quality of evidence and strength of recommendations, To2rpido’s impact was downgraded because of high risk of bias. This review [4] continues to recommend “starting with a lower oxygen concentration (21–30%) compared to higher oxygen concentration (60–100%)” whilst highlighting many gaps in our current knowledge.
The use of end-tidal CO2 (ETCO2) detection was not recommended because the guidelines, and Newborn Life Support (NLS) course, focus on airwa...
Show MoreDear Editor,
Show MoreWe read with great interest the network meta-analysis performed by Zeng et al [1]. The authors investigated the comparative efficacy and safety of different corticosteroids in the prevention of bronchopulmonary dysplasia in preterm infants. They included 47 RCTs with 6747 participants. We have several concerns about the study.
First, it looks that the authors are unfamiliar with the procedures of network meta-analysis because there were obvious mistakes. Figure 1 in the study was network plot of different corticosteroids. In Figure 1, the circle size should be proportional to the sample size randomised to each intervention [2]. The line width should be proportional to the study numbers of each direct comparison. However, the circle size was not proportional to the sample size in Figure 1. The line width between dexamethasone (high dose) and placebo also seems inadequate.
Second, various statistical methods or plots have been suggested to assist interpreting the results of network meta-analysis [3]. However, many of them were not performed or presented in this study. For example, since there were direct estimates (i.e., results of pairwise meta-analysis) and indirect estimates (i.e., results of network meta-analysis), the inconsistency between them should be assessed and explored because important inconsistency could threaten the validity of the results. Besides, the authors also didn’t assess small-study effects. Small-study effects could mat...
There seems to be a descrepency regarding the number of babies intubatec in two groups. 56 babies were intubated in high tidal volume group against 14 intubated in the low tidal volume group as per the article. I wondering whether it might have contributed to the high incidence of IVH in the high tidal volume group.
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