Dear Editor,
We read with interest the paper from our colleagues in Toronto on the possible association between the use of diazoxide treatment for hypoglycemia and the onset of necrotizing enterocolitis (NEC). We wish to share our single-center experience on diazoxide and we beg to differ with the authors. Our NICU is a tertiary care center from Midwest Canada that has the least incidence of NEC across all the centers in Canada as per Canadian Neonatal Network (CNN) database. For nearly 2 decades, we have been using diazoxide in our unit, in the treatment of persistent neonatal hypoglycemia among intra-uterine growth retardation, small-for-gestational age, infant of a diabetic mother, and transient hyperinsulinemic hypoglycemia neonates.
Our neonates are comparable to Toronto population, with prematurity, and other risk factors. We have used both moderate doses (5-10mg/kg/day) and higher doses (maximum up to 15mg/kg/day) in 3 divided doses in our practice. Over the last 10 years (between the years 2010-2020), 164 neonates have received diazoxide treatment in our NICU and none of them have had NEC as a complication of treatment during or after the therapy. Common side-effects of diazoxide in infants and children include nausea, vomiting, loss of appetite, headache, dizziness, stomach pain or upset, diarrhea, changes in sense of taste, hypertrichosis (especially in women and children), anxiety, weakness, pruritus or skin rash. We agree as the authors mentioned on...
Dear Editor,
We read with interest the paper from our colleagues in Toronto on the possible association between the use of diazoxide treatment for hypoglycemia and the onset of necrotizing enterocolitis (NEC). We wish to share our single-center experience on diazoxide and we beg to differ with the authors. Our NICU is a tertiary care center from Midwest Canada that has the least incidence of NEC across all the centers in Canada as per Canadian Neonatal Network (CNN) database. For nearly 2 decades, we have been using diazoxide in our unit, in the treatment of persistent neonatal hypoglycemia among intra-uterine growth retardation, small-for-gestational age, infant of a diabetic mother, and transient hyperinsulinemic hypoglycemia neonates.
Our neonates are comparable to Toronto population, with prematurity, and other risk factors. We have used both moderate doses (5-10mg/kg/day) and higher doses (maximum up to 15mg/kg/day) in 3 divided doses in our practice. Over the last 10 years (between the years 2010-2020), 164 neonates have received diazoxide treatment in our NICU and none of them have had NEC as a complication of treatment during or after the therapy. Common side-effects of diazoxide in infants and children include nausea, vomiting, loss of appetite, headache, dizziness, stomach pain or upset, diarrhea, changes in sense of taste, hypertrichosis (especially in women and children), anxiety, weakness, pruritus or skin rash. We agree as the authors mentioned on the occurrence of transient fluid retention, pulmonary edema, elevated pulmonary pressures, and brief oxygen dependency during and after the diazoxide treatment as side effects in neonates.
The authors have highlighted that seven (13%) out of fifty-five neonates developed NEC after diazoxide treatment. [1] And of the 7 patients, one patient was exposed to octreotide. [1] Octreotide has already been known to have proven hemodynamic side-effects on splanchnic circulation, thereby predisposing these vulnerable population leading to NEC. When the baby is receiving octreotide, there could have been a cascade of hemodynamic changes in the gut which could be monitored by NIRS or abdominal Doppler studies to assess gut blood flow. As the authors mention, Gray KD et al. reported 1066 neonates treated with diazoxide for hypoglycemia, less than 1% of neonates developed NEC. In our center, we decided to use diazoxide as a monotherapy in the treatment of neonatal hypoglycemia. Diazoxide did not cause any alterations in the intestinal blood flow which was monitored by near-infrared spectroscopy (NIRS). According to Table.3 in the paper, there were no significant difference between the diazoxide initial dose and maximum dose used between the NEC vs. no NEC group.
Thus, diazoxide has been used in our center successfully with no major side-effects. It also helped in shortening the duration of stay and cost of treatment substantially thereby reducing the burden on our provincial healthcare system.
Kaarthigeyan Kalaniti1, Veronica Samedi1, Neil Wonko1, Sibasis Daspal1
1Division of Neonatology, Dept. of Pediatrics,
Jim Pattison Children’s Hospital,
University of Saskatchewan, Saskatoon, SK, Canada
E-mail: vmsamedi@gmail.com
References:
1. Prado LA, Castro M, Weisz DE, et al. Arch Dis Child Fetal Neonatal Ed. 2020; 0: F1–F5.
Dear Editor,
As an emerging medical education researcher with an interest in video, and as a practising anaesthetist, I read O’Shea et al’s article on neonatal videolaryngoscopy[1] with great interest. I applaud and encourage the authors for their interest in medical education, which I believe underpins medicine’s ability to do the best for our patients. However, I wish to draw attention to two points that I believe should be addressed for future papers covering this topic.
1. The authors in this paper use the words “conventional laryngoscope blades” to describe direct laryngoscopy without video feed. This assumes that what is conventional for the authors is conventional for the audience. In this paper I had assumed that “conventional” to a neonatologist would be a Miller (straight) blade, and that the video laryngoscope blade was a Macintosh blade because it was curved. However, after reviewing Kirolos and O’Shea[2], I recognised that both types of blade used in the study were possibly Miller blade variants, although I cannot know for certain. I feel it would be better in future papers that the term “conventional largynoscope blade” be avoided and the specific type of blades be specified.
2. Grounded theory is cited as the methodology used for the free text response analysis. I wish to point out that there are several variants of grounded theory with different methodologies following the divergence between the two original authors, Glasser and Strauss[3]...
Dear Editor,
As an emerging medical education researcher with an interest in video, and as a practising anaesthetist, I read O’Shea et al’s article on neonatal videolaryngoscopy[1] with great interest. I applaud and encourage the authors for their interest in medical education, which I believe underpins medicine’s ability to do the best for our patients. However, I wish to draw attention to two points that I believe should be addressed for future papers covering this topic.
1. The authors in this paper use the words “conventional laryngoscope blades” to describe direct laryngoscopy without video feed. This assumes that what is conventional for the authors is conventional for the audience. In this paper I had assumed that “conventional” to a neonatologist would be a Miller (straight) blade, and that the video laryngoscope blade was a Macintosh blade because it was curved. However, after reviewing Kirolos and O’Shea[2], I recognised that both types of blade used in the study were possibly Miller blade variants, although I cannot know for certain. I feel it would be better in future papers that the term “conventional largynoscope blade” be avoided and the specific type of blades be specified.
2. Grounded theory is cited as the methodology used for the free text response analysis. I wish to point out that there are several variants of grounded theory with different methodologies following the divergence between the two original authors, Glasser and Strauss[3]. However, in this article there is no reference for the type of grounded theory that is used. This leaves me and other readers in a quandry – If we wanted to repeat this study to verify its results, what variant of grounded theory should we use? For just as statistical quantitative methodologies are explained and referenced, I believe that qualitative methodologies used should also be referenced for academic rigour and reproducibility.
In summary, I hope that this feedback will be accepted in the spirit in which I give it – to improve the overall rigour of the medical education literature.
Yours sincerely,
Dr Andrew Huang
[1] J. E. O’Shea, S. Kirolos, M. Thio, C. O. F. Kamlin, and P. G. Davis, ‘Neonatal videolaryngoscopy as a teaching aid: the trainees’ perspective’, Archives of disease in childhood. Fetal and neonatal edition, vol. 106, no. 2, pp. 168–171, 2021, doi: 10.1136/archdischild-2020-319619.
[2] S. Kirolos and J. E. O’Shea, ‘Comparison of conventional and videolaryngoscopy blades in neonates’, Archives of Disease in Childhood - Fetal and Neonatal Edition, vol. 105, no. 1, pp. 94–97, Jan. 2020, doi: 10.1136/archdischild-2018-315644.
[3] ‘Grounded theory’, Wikipedia. Jan. 17, 2021. Accessed: May 20, 2021. [Online]. Available: https://en.wikipedia.org/w/index.php?title=Grounded_theory&oldid=1000964355
We thank Dr. Khashu for his comments on our article Metabolic bone disease of prematurity: causes, recognition, prevention, treatment and long-term consequences.
Below we provide responses to his comments.
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.
Response: Our suggested approach on management of Metabolic Bone Disease of Prematurity (MBDP) is underpinned by pathophysiology of this disorder. The case discussed is not an anecdotal case but represents many such cases referred to our service. In all age groups calcipaenic state (Calcium deficiency) causes increase in PTH secretion while phosphopaenic states (inadequate Phosphate absorption from diet or primary urinary phosphate leak) do not. Therefore our approach is to measure PTH to guide mineral supplementation and more specifically to maintain appropriate oral Calcium (Ca) to Phosphate (PO4) ratio for adequate mineralisation of bones. It is our observation that PTH is not routinely measured in MBDP but, there are publications where PTH has been measured...
We thank Dr. Khashu for his comments on our article Metabolic bone disease of prematurity: causes, recognition, prevention, treatment and long-term consequences.
Below we provide responses to his comments.
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.
Response: Our suggested approach on management of Metabolic Bone Disease of Prematurity (MBDP) is underpinned by pathophysiology of this disorder. The case discussed is not an anecdotal case but represents many such cases referred to our service. In all age groups calcipaenic state (Calcium deficiency) causes increase in PTH secretion while phosphopaenic states (inadequate Phosphate absorption from diet or primary urinary phosphate leak) do not. Therefore our approach is to measure PTH to guide mineral supplementation and more specifically to maintain appropriate oral Calcium (Ca) to Phosphate (PO4) ratio for adequate mineralisation of bones. It is our observation that PTH is not routinely measured in MBDP but, there are publications where PTH has been measured and was found to be useful, both in diagnosis and management of MBDP1-5. Besides us Moreira et al have also demonstrated usefulness of PTH measurement and treatment using oral calcium supplements2. Oral phosphate supplementation reduces ionized calcium and therefore increases parathyroid hormone concentration. This pathophysiological concept is further elucidated in recent published case in Archives of Disease in Childhood education and practice section where pharmacological dose of oral phosphate in MBDP caused hypocalcaemia6. Our advice is to maintain oral Ca to PO4 ratio as unopposed supplementation with PO4 can cause secondary hyperparathyroidism and worsening of MBDP.
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?
Response: We agree that data on normal ranges of PTH in preterm infants was derived from 20 preterm neonates but, with 134 separate measurements7. This study is well conducted and in healthy neonates, PTH concentration using third-generation immunoassays demonstrated values similar to adult reference ranges with authors concluding that values above this should be considered as secondary hyperparathyroidism. Unlike serum PO4, Ca concentration is tightly maintained within a narrow range in all age groups and it would therefore appear that PTH, which is the primary hormone for Ca homeostasis, is also maintained within the normal range in all age groups. We believe therefore that current reference ranges of PTH in combination with measurement of serum Ca, PO4 and Alkaline Phosphatase are sensitive indicator of MBDP and will allow us to guide management with appropriate mineral supplementation. Of course a larger study will be most welcome specially looking at various gestational ages and corrected ages in premature infants taking into consideration infant’s dietary Ca intake and serum Vitamin D concentration.
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.
Response: The purpose of these images was to demonstrate consequences of secondary hyperparathyroidism when Ca to PO4 mineral ratio is not maintained. These manifestations are generalised and affects all long bones of infant. Through these images we have demonstrated improvement in bone mineralisation, healing of periosteal elevation and rickets following treatment with oral calcium and vitamin D supplementation. Even though, these images are of different arms, healing of above manifestations of MBDP are clearly demonstrated.
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?
Response: Please also refer to our response to comment 2. We agree that a larger dataset in preterm neonates would be appropriate. Given challenges of undertaking this study in sick preterm infants, we would have to rely on above mentioned well conducted study7 which has demonstrated that adult normative ranges are applicable in preterm neonates. In our clinical practise we have always found measurement of PTH extremely useful in diagnosis and monitoring of treatment in all cases of MBDP. Our clinical approach of maintaining oral Ca to PO4 ratio in management of rickets has allowed normalisation of serum PTH, PO4 and ALP, healing of rickets and prevented secondary hyperparathyroidism and associate complications such as hypocalcaemia and fractures.
References:
Lothe A, Sinn J, Stone M. Metabolic bone disease of prematurity and secondary hyperparathyroidism. J Paediatr Child Health. 2011;47(8):550–553.
Moreira A, February M, Geary C. Parathyroid hormone levels in neonates with suspected osteopenia. J Paediatr Child Health. 2013;49(1):E12–E16.
Yes¸iltepe Mutlu G, Kırmızıbekmez H, Ozsu E, et al. Metabolic bone disease of prematurity: report of four cases. J Clin Res Pediatr Endocrinol. 2014;6(2):111–115.
Dowa Y, Kawai M, Kanazawa H, et al. Screening for secondary hyperparathyroidism in preterm infants. Pediatr Int. 2016;58(10):988–992.
Patel M, Housley D, Ossuetta I. Serial serum parathormone (PTH) as a marker for monitoring metabolic bone disease of prematurity. Arch Dis Child. 2008;93:ps323.
Liddicoat INM, Tighe MP. Supplementation in hypophosphataemic rickets: the bare bones of management. Arch Dis Child Educ Pract Ed 2019;104:207-210. Matejek T ,
Navratilova M , Zaloudkova L , et al. Parathyroid hormone - reference values and association with other bone metabolism markers in very low birth weight infants - pilot study. J Matern Fetal Neonatal Med 2018:1–8.
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?
The reported findings that some MRSOPA corrective steps actually made matters worse (1) should be a wake-up call to those teaching neonatal resuscitation (NRP), especially as many components of the algorithm are not evidence based and have never been validated.
I wish to briefly report on two adverse outcomes which occurred on Vancouver Island at separate sites and at separate times, both following the introduction of the MRSOPA algorithm. Both infants were delivered at term by C Section under maternal general anesthetic. One was a preplanned elective C Section, the other for failure to progress with no concerns with the fetal heart tracing. There was no meconium present in the amniotic fluid. Both infants were depressed at birth but with palpable heartbeat. For both infants, there was difficulty in establishing effective ventilation. When intubation was eventually achieved, there was no colour change with CO2 detector, resulting in removal and resumption of bag-mask ventilation. The Neopuff (Fisher & Paykel) T piece was used in both cases and pressures were initially set at 20/5cm H20, as per NRP guidelines. However pressure increases occurred late. One baby had completely normal arterial cord gases. The other had an arterial cord pH 7.17.
Following a prolonged but eventually successful resuscitation, both infants were cooled for 72hours. One infant required transport to a level 3 site and subsequently did well. The other child did poorly. That child now...
The reported findings that some MRSOPA corrective steps actually made matters worse (1) should be a wake-up call to those teaching neonatal resuscitation (NRP), especially as many components of the algorithm are not evidence based and have never been validated.
I wish to briefly report on two adverse outcomes which occurred on Vancouver Island at separate sites and at separate times, both following the introduction of the MRSOPA algorithm. Both infants were delivered at term by C Section under maternal general anesthetic. One was a preplanned elective C Section, the other for failure to progress with no concerns with the fetal heart tracing. There was no meconium present in the amniotic fluid. Both infants were depressed at birth but with palpable heartbeat. For both infants, there was difficulty in establishing effective ventilation. When intubation was eventually achieved, there was no colour change with CO2 detector, resulting in removal and resumption of bag-mask ventilation. The Neopuff (Fisher & Paykel) T piece was used in both cases and pressures were initially set at 20/5cm H20, as per NRP guidelines. However pressure increases occurred late. One baby had completely normal arterial cord gases. The other had an arterial cord pH 7.17.
Following a prolonged but eventually successful resuscitation, both infants were cooled for 72hours. One infant required transport to a level 3 site and subsequently did well. The other child did poorly. That child now has a profound permanent brain injury, attributed to perinatal hypoxic ischaemic encephalopathy.
I am concerned that these cases may not be isolated case reports but rather part of an emerging problem with infant resuscitation and the NRP MRSOPA algorithm. The P (for pressure increase) and the A (for alternative airway) are well down the pathway of interventions and follow useless and possibly counterproductive manoeuvers, such as opening the mouth and suctioning. Practitioners may also forget that there are now two “P”s (MR SOPPA), so may only increase pressures to 25cm (why do we start at pressures of 20cm for term babies?) before attempting an alternative airway. Further, since tracheal intubation for meconium was removed from the NRP algorithm, there has been a decrease in both confidence and skill when performing this procedure. Although a laryngeal mask airway is easy to insert, many practitioners have never used one.
If any readers are aware of similar cases, they are encouraged to contact (with patient identifiers removed) me in confidence. If we see any evidence of an emerging problem, we can share our findings with International Consensus on Cardiopulmonary Resuscitation Committee (ILCOR).
1. Corrective steps to enhance ventilation in the delivery room: Yang KC, Pas AB, Weinberg DD, et al. Arch Dis Child Fetal Neonatal Ed 2020;105:F605–F608
Hollebrandse et al are to be congratulated on achieving such a high follow-up rate at 8 years in a large cohort of preterm infants with intraventricular haemorrhage (IVH). Long-term outcomes related to specific cUS findings are increasingly important as many significant if more subtle neurodevelopmental problems are not detected at earlier follow-up.
It is reassuring that children with the milder grades of IVH had intellectual outcomes similar to the no-IVH group but of concern is the report of significant motor deficits and cerebral palsy (CP) following grades 1 and 2 IVH. However the outcomes given may not solely be related to IVH but to other pathologies notably cystic periventricular leukomalacia (cPVL) a well-known predictor of motor deficits and CP.[1,2] cPVL was found in 6% and 4% of the children with grades 1 and 2 IVH and 13% and 25% of those with grades 3 and 4 IVH. The authors neither adjust for this pathology, saying that “cPVL may lie along the causal pathway between IVH and adverse outcomes”, nor do they give evidence to support this statement. Indeed the contribution of cPVL to outcomes is not discussed or mentioned in the abstract. We are not aware of evidence that low grade IVH is in a causal pathway to cPVL, and suggested associations between cPVL and higher grades of IVH were based on studies using infrequent ultrasound protocols and without MRI scanning at term equivalent age. [3,4] We are aware of preterm infants who develop late-onset c-PVL no...
Hollebrandse et al are to be congratulated on achieving such a high follow-up rate at 8 years in a large cohort of preterm infants with intraventricular haemorrhage (IVH). Long-term outcomes related to specific cUS findings are increasingly important as many significant if more subtle neurodevelopmental problems are not detected at earlier follow-up.
It is reassuring that children with the milder grades of IVH had intellectual outcomes similar to the no-IVH group but of concern is the report of significant motor deficits and cerebral palsy (CP) following grades 1 and 2 IVH. However the outcomes given may not solely be related to IVH but to other pathologies notably cystic periventricular leukomalacia (cPVL) a well-known predictor of motor deficits and CP.[1,2] cPVL was found in 6% and 4% of the children with grades 1 and 2 IVH and 13% and 25% of those with grades 3 and 4 IVH. The authors neither adjust for this pathology, saying that “cPVL may lie along the causal pathway between IVH and adverse outcomes”, nor do they give evidence to support this statement. Indeed the contribution of cPVL to outcomes is not discussed or mentioned in the abstract. We are not aware of evidence that low grade IVH is in a causal pathway to cPVL, and suggested associations between cPVL and higher grades of IVH were based on studies using infrequent ultrasound protocols and without MRI scanning at term equivalent age. [3,4] We are aware of preterm infants who develop late-onset c-PVL not related to an initial low grade IVH but following (Gram-negative) sepsis or necrotising enterocolitis occurring later in the neonatal period.
Compared to several other studies, a high percentage of infants in this study developed CP (8% with no IVH, and 15, 18, 26 and 75% with grades 1-4 IVH). The higher levels of CP than generally expected for grades 1 and 2 IVH [5,6] may partly be explained by the presence of cPVL. Additionally there may have been non-cystic white matter injury e.g. punctate white matter lesions, cerebellar lesions or strokes that were not detected with the imaging protocol used. The statement "Our study adds to a growing understanding of the negative impact of low grade IVH on motor development" fails to adjust the findings for other lesion(s) known to lead to impaired motor development.
We also find the rates of CP in children with grades 3 and 4 IVH high. These may in part be related to care pathways chosen and the timing of treatment of post-haemorrhagic ventricular dilatation but no information is given about this.[7] One might expect about 50-60% of preterm infants with grade 4 IVH to develop a hemiplegia whilst here it is 75% perhaps influenced by the fact that 25% also had cPVL.
Another unexpected and worrying finding is that the severity of CP was the same in children with lower and higher grades of IVH. This could be due to the inclusion of infants with co-existing c-PVL or other lesions. It is unfortunate that no MRI findings are reported to substantiate the cUS findings particularly in infants with CP following low-grade IVH.
This paper may well be used by neonatologists to give prognoses following IVH in the first week after birth. We are concerned that these data will worry parents unnecessarily, especially those of infants with isolated low-grade IVH. Whilst it is fair to tell parents that other lesions may become apparent or develop we need to distinguish between outcomes due to findings seen at the time of scanning and those related to a potential pathology not yet seen and perhaps developing following unrelated clinical problems.
Yours sincerely
Frances Cowan, Floris Groenendaal and Linda S de Vries
Author affiliations:
Prof Frances M Cowan PhD FRCPCH
Dept. of Paediatrics
Hammersmith Hospital
Imperial College London
W12 0HS, UK
Email f.cowan@imperial.ac.uk
Dr Floris Groenendaal MD PhD and Prof Linda S de Vries MD PhD
Wilhelmina Children’s Hospital,
University Medical Centre Utrecht,
KE 04.123.1, PO Box 85090,
3508 AB Utrecht, Netherlands
References
1. Martinez-Biarge M, Groenendaal F, Kersbergen KJ, Benders MJNL, Foti F, van Haastert IC, Cowan FM, de Vries LS. Neurodevelopmental Outcomes in Preterm Infants with White Matter Injury Using a New MRI Classification. Neonatology. 2019;116(3):227-235
2. van Haastert IC, Groenendaal F, Uiterwaal CS, Termote JU, van der Heide-Jalving M, Eijsermans MJ, Gorter JW, Helders PJ, Jongmans MJ, de Vries LS. Decreasing incidence and severity of cerebral palsy in prematurely born children. J Pediatr. 2011 Jul;159(1):86-91.e1
3. Kusters CDJ, Chen ML, Follett PL Dammann O. "Intraventricular" hemorrhage and cystic periventricular leukomalacia in preterm infants: How are they related? J Child Neurol 2009; 24:1158-1170.
4. Kuban K, Sanocka U, Leviton A, Allred EN, Pagano M, Dammann O, et al. White matter disorders of prematurity: association with intraventricular hemorrhage and ventriculomegaly. J Pediatr 1999; 134:539-546.
5. Payne AH, Hintz SR, Hibbs AM, Walsh MC, Vohr BR, Bann CM, Wilson-Costello DE; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network: Neurodevelopmental outcomes of extremely low-gestational age neonates with low-grade periventricular intraventricular hemorrhage. JAMA Pediatr 2013;167:451–459.
6. Reubsaet P, Brouwer AJ, van Haastert IC, Brouwer MJ, Koopman C, Groenendaal F, de Vries LS. The Impact of Low-Grade Germinal Matrix-Intraventricular Hemorrhage on Neurodevelopmental Outcome of Very Preterm Infants. Neonatology 2017;112(3):203-210.
7. Leijser LM, Miller SP, van Wezel-Meijler G, Brouwer AJ, Traubici J, van Haastert IC, Whyte HE, Groenendaal F, Kulkarni AV, Han KS, Woerdeman PA, Church PT, Kelly EN, van Straaten HLM, Ly LG, de Vries LS. Posthemorrhagic ventricular dilatation in preterm infants: When best to intervene? Neurology. 2018;90(8):e698-e706
Footnotes
• Contributors: FMC, FD and LdeV contributed equally to the letter
• Funding: The authors have not declared a specific funding agency in the public, commercial or not-for-profit sectors.
• Competing interests: None declared.
• Provenance and peer review: Not commissioned.
• Patient consent for publication: Not required.
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
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.
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 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.
Dear Editor,
Show MoreWe read with interest the paper from our colleagues in Toronto on the possible association between the use of diazoxide treatment for hypoglycemia and the onset of necrotizing enterocolitis (NEC). We wish to share our single-center experience on diazoxide and we beg to differ with the authors. Our NICU is a tertiary care center from Midwest Canada that has the least incidence of NEC across all the centers in Canada as per Canadian Neonatal Network (CNN) database. For nearly 2 decades, we have been using diazoxide in our unit, in the treatment of persistent neonatal hypoglycemia among intra-uterine growth retardation, small-for-gestational age, infant of a diabetic mother, and transient hyperinsulinemic hypoglycemia neonates.
Our neonates are comparable to Toronto population, with prematurity, and other risk factors. We have used both moderate doses (5-10mg/kg/day) and higher doses (maximum up to 15mg/kg/day) in 3 divided doses in our practice. Over the last 10 years (between the years 2010-2020), 164 neonates have received diazoxide treatment in our NICU and none of them have had NEC as a complication of treatment during or after the therapy. Common side-effects of diazoxide in infants and children include nausea, vomiting, loss of appetite, headache, dizziness, stomach pain or upset, diarrhea, changes in sense of taste, hypertrichosis (especially in women and children), anxiety, weakness, pruritus or skin rash. We agree as the authors mentioned on...
Dear Editor,
Show MoreAs an emerging medical education researcher with an interest in video, and as a practising anaesthetist, I read O’Shea et al’s article on neonatal videolaryngoscopy[1] with great interest. I applaud and encourage the authors for their interest in medical education, which I believe underpins medicine’s ability to do the best for our patients. However, I wish to draw attention to two points that I believe should be addressed for future papers covering this topic.
1. The authors in this paper use the words “conventional laryngoscope blades” to describe direct laryngoscopy without video feed. This assumes that what is conventional for the authors is conventional for the audience. In this paper I had assumed that “conventional” to a neonatologist would be a Miller (straight) blade, and that the video laryngoscope blade was a Macintosh blade because it was curved. However, after reviewing Kirolos and O’Shea[2], I recognised that both types of blade used in the study were possibly Miller blade variants, although I cannot know for certain. I feel it would be better in future papers that the term “conventional largynoscope blade” be avoided and the specific type of blades be specified.
2. Grounded theory is cited as the methodology used for the free text response analysis. I wish to point out that there are several variants of grounded theory with different methodologies following the divergence between the two original authors, Glasser and Strauss[3]...
Dear Editors,
Archives of Disease in Childhood
We thank Dr. Khashu for his comments on our article Metabolic bone disease of prematurity: causes, recognition, prevention, treatment and long-term consequences.
Below we provide responses to his comments.
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.
Response: Our suggested approach on management of Metabolic Bone Disease of Prematurity (MBDP) is underpinned by pathophysiology of this disorder. The case discussed is not an anecdotal case but represents many such cases referred to our service. In all age groups calcipaenic state (Calcium deficiency) causes increase in PTH secretion while phosphopaenic states (inadequate Phosphate absorption from diet or primary urinary phosphate leak) do not. Therefore our approach is to measure PTH to guide mineral supplementation and more specifically to maintain appropriate oral Calcium (Ca) to Phosphate (PO4) ratio for adequate mineralisation of bones. It is our observation that PTH is not routinely measured in MBDP but, there are publications where PTH has been measured...
Show MoreI 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...
The reported findings that some MRSOPA corrective steps actually made matters worse (1) should be a wake-up call to those teaching neonatal resuscitation (NRP), especially as many components of the algorithm are not evidence based and have never been validated.
Show MoreI wish to briefly report on two adverse outcomes which occurred on Vancouver Island at separate sites and at separate times, both following the introduction of the MRSOPA algorithm. Both infants were delivered at term by C Section under maternal general anesthetic. One was a preplanned elective C Section, the other for failure to progress with no concerns with the fetal heart tracing. There was no meconium present in the amniotic fluid. Both infants were depressed at birth but with palpable heartbeat. For both infants, there was difficulty in establishing effective ventilation. When intubation was eventually achieved, there was no colour change with CO2 detector, resulting in removal and resumption of bag-mask ventilation. The Neopuff (Fisher & Paykel) T piece was used in both cases and pressures were initially set at 20/5cm H20, as per NRP guidelines. However pressure increases occurred late. One baby had completely normal arterial cord gases. The other had an arterial cord pH 7.17.
Following a prolonged but eventually successful resuscitation, both infants were cooled for 72hours. One infant required transport to a level 3 site and subsequently did well. The other child did poorly. That child now...
Hollebrandse et al are to be congratulated on achieving such a high follow-up rate at 8 years in a large cohort of preterm infants with intraventricular haemorrhage (IVH). Long-term outcomes related to specific cUS findings are increasingly important as many significant if more subtle neurodevelopmental problems are not detected at earlier follow-up.
It is reassuring that children with the milder grades of IVH had intellectual outcomes similar to the no-IVH group but of concern is the report of significant motor deficits and cerebral palsy (CP) following grades 1 and 2 IVH. However the outcomes given may not solely be related to IVH but to other pathologies notably cystic periventricular leukomalacia (cPVL) a well-known predictor of motor deficits and CP.[1,2] cPVL was found in 6% and 4% of the children with grades 1 and 2 IVH and 13% and 25% of those with grades 3 and 4 IVH. The authors neither adjust for this pathology, saying that “cPVL may lie along the causal pathway between IVH and adverse outcomes”, nor do they give evidence to support this statement. Indeed the contribution of cPVL to outcomes is not discussed or mentioned in the abstract. We are not aware of evidence that low grade IVH is in a causal pathway to cPVL, and suggested associations between cPVL and higher grades of IVH were based on studies using infrequent ultrasound protocols and without MRI scanning at term equivalent age. [3,4] We are aware of preterm infants who develop late-onset c-PVL no...
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 MoreWe 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-...
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 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...
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