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.
In response to: "Early lung ultrasound affords little to the prediction of bronchopulmonary dysplasia".
We read with great interest the article by Dr Woods et al (1) that adds evidence to recent, large multicenter studies on lung ultrasound (LUS) as a predictive tool for bronchopulmonary dysplasia (BPD) (2-4). These studies, performed on a total of more than 600 infants, stem from a validated scoring system whose signs represent a progressive decrease in lung aeration in standardized ultrasound views (5). Notably, this approach is also well established in adult critical care (6).
The grading system adopted by Dr Woods and coworkers, has not been validated and its highest scores do not correspond to less air in the lung and therefore to a more severe pulmonary disease. Also, rather than the conventional sum of scores, Dr Woods et al. calculate a two-decimals mean score that may undermine the technique discrimination. None of these choices have ever been made for any other LUS scores, neither in neonates nor in older patients, despite ultrasound semiology and statistics needed to evaluate the predictive power are always the same (6). These factors may undermine the LUS prediction power for BPD.
Moreover, the authors needed a full ROC procedure to perform a formal diagnostic accuracy analysis, but even then, its strength would have been questionable with only 7 out 96 infants suffering from moderate-to-severe BPD (7) as target condition. This smal...
In response to: "Early lung ultrasound affords little to the prediction of bronchopulmonary dysplasia".
We read with great interest the article by Dr Woods et al (1) that adds evidence to recent, large multicenter studies on lung ultrasound (LUS) as a predictive tool for bronchopulmonary dysplasia (BPD) (2-4). These studies, performed on a total of more than 600 infants, stem from a validated scoring system whose signs represent a progressive decrease in lung aeration in standardized ultrasound views (5). Notably, this approach is also well established in adult critical care (6).
The grading system adopted by Dr Woods and coworkers, has not been validated and its highest scores do not correspond to less air in the lung and therefore to a more severe pulmonary disease. Also, rather than the conventional sum of scores, Dr Woods et al. calculate a two-decimals mean score that may undermine the technique discrimination. None of these choices have ever been made for any other LUS scores, neither in neonates nor in older patients, despite ultrasound semiology and statistics needed to evaluate the predictive power are always the same (6). These factors may undermine the LUS prediction power for BPD.
Moreover, the authors needed a full ROC procedure to perform a formal diagnostic accuracy analysis, but even then, its strength would have been questionable with only 7 out 96 infants suffering from moderate-to-severe BPD (7) as target condition. This small number of patients with the target disease reduces the diagnostic accuracy of any exam performed for an early prediction.
Finally, we agree with Dr Woods and colleagues that LUS is not a silver bullet, but adequate methodology should be followed to investigate it. According to data produced with this methodology LUS has a significant power for BPD prediction.
REFERENCES
1. Woods PL, Stoecklin B, Woods A, Gill AW. Early lung ultrasound affords little to the prediction of bronchopulmonary dysplasia. Arch Dis Child Fetal Neonatal Ed. 2021 May 14;fetalneonatal-2020-320830.
2. Raimondi F, Migliaro F, Corsini I, Meneghin F, Dolce P, Pierri L, et al. Lung Ultrasound Score Progress in Neonatal Respiratory Distress Syndrome. Pediatrics. 2021 Apr;147(4):e2020030528.
3. Alonso-Ojembarrena A, Serna-Guerediaga I, Aldecoa-Bilbao V, Gregorio-Hernández R, Alonso-Quintela P, Concheiro-Guisán A, et al. The Predictive Value of Lung Ultrasound Scores in Developing Bronchopulmonary Dysplasia. Chest. 2021 Mar;S0012369221004682.
4. Loi B, Vigo G, Baraldi E, Raimondi F, Carnielli VP, Mosca F, et al. Lung Ultrasound to Monitor Extremely Preterm Infants and Predict BPD: Multicenter Longitudinal Cohort Study. Am J Respir Crit Care Med. 2020 Dec 22;rccm.202008-3131OC.
5. Brat R, Yousef N, Klifa R, Reynaud S, Shankar Aguilera S, De Luca D. Lung Ultrasonography Score to Evaluate Oxygenation and Surfactant Need in Neonates Treated With Continuous Positive Airway Pressure. JAMA Pediatr. 2015 Aug;169(8):e151797. doi: 10.1001/jamapediatrics.2015.1797.
6. Mongodi S, De Luca D, Colombo A, Stella A, Santangelo E, Corradi F, Gargani L, Rovida S, Volpicelli G, Bouhemad B, Mojoli F. Quantitative Lung Ultrasound: Technical Aspects and Clinical Applications. Anesthesiology. 2021 Jun 1;134(6):949-965. doi: 10.1097/ALN.0000000000003757.
7. Higgins RD, Jobe AH, Koso-Thomas M, Bancalari E, Viscardi RM, Hartert TV, et al. Bronchopulmonary Dysplasia: Executive Summary of a Workshop. The Journal of Pediatrics. 2018 Jun;197:300–8.
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
“Parenteral nutrition for preterm infants: Correcting for arachidonic and
docosahexaenoic acid may not suffice” by Bernard et al. regarding the publication:
Frazer LC, Martin CR. Parenteral lipid emulsions in the preterm infant: current issues
and controversies. Arch Dis Child Fetal Neonatal Ed. 2021 Jan 29: fetalneonatal-
2020-319108. doi: 10.1136/archdischild-2020-319108. Epub ahead of print. PMID:
33514630.
Lauren C. Frazer1,2, Camilia R. Martin2,3,4
1Division of Newborn Medicine, Boston Children’s Hospital, Boston, MA, USA
2Department of Pediatrics, Harvard Medical School, Boston, MA, USA
3Division of Translational Research, Beth Israel Deaconess Medical Center, Boston, MA, USA 4Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, MA, USA
Correspondence: cmartin1@bidmc.harvard.edu
We would like to thank Bernhard and colleagues for their thoughtful letter “Parenteral nutrition for preterm infants: Correcting for arachidonic and docosahexaenoic acid may not suffice” written in response to our review. The authors of the letter raised important issues regarding the lack of data surrounding the optimal balance of arachidonic (ARA) and docosahexaenoic acid (DHA) that should be administered...
“Parenteral nutrition for preterm infants: Correcting for arachidonic and
docosahexaenoic acid may not suffice” by Bernard et al. regarding the publication:
Frazer LC, Martin CR. Parenteral lipid emulsions in the preterm infant: current issues
and controversies. Arch Dis Child Fetal Neonatal Ed. 2021 Jan 29: fetalneonatal-
2020-319108. doi: 10.1136/archdischild-2020-319108. Epub ahead of print. PMID:
33514630.
Lauren C. Frazer1,2, Camilia R. Martin2,3,4
1Division of Newborn Medicine, Boston Children’s Hospital, Boston, MA, USA
2Department of Pediatrics, Harvard Medical School, Boston, MA, USA
3Division of Translational Research, Beth Israel Deaconess Medical Center, Boston, MA, USA 4Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, MA, USA
Correspondence: cmartin1@bidmc.harvard.edu
We would like to thank Bernhard and colleagues for their thoughtful letter “Parenteral nutrition for preterm infants: Correcting for arachidonic and docosahexaenoic acid may not suffice” written in response to our review. The authors of the letter raised important issues regarding the lack of data surrounding the optimal balance of arachidonic (ARA) and docosahexaenoic acid (DHA) that should be administered to preterm neonates by these emulsions as well as the inadequacy of current lipid emulsions in providing other components such as myristic acid and choline. While we focused on long chain polyunsaturated fatty acids in our review, we agree that lipid emulsions are a complex matrix of components beyond ARA and DHA and highlighted this in Table 3 under Formulation when discussing current research gaps. We chose to highlight the fatty acid balance in this concise review because, in our experience, this topic largely drives the motivation in selecting lipid emulsions by providers in the neonatal intensive care unit. Advanced analytical methods from detection to data analysis are now available to take a comprehensive approach in understanding the metabolic influence of complex lipid emulsions in neonatal development and disease risk. Such studies are a necessary step in developing nutritional products designed to meet the unique needs of preterm infants encompassing those highlighted by Bernhard and colleagues.
Thank you,
Lauren C. Frazer, MD PhD
Camilia R. Martin, MD MS
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.
We read with interest results from the Hypotension in Preterm Infants (HIP) trial by Dempsey et al.1 Unfortunately this multicentre randomised controlled trial (RCT) could not provide robust conclusions. Enrolment was limited to 58 of the planned 830 infants, 7% of those screened, attributed to strict inclusion criteria and recruitment challenges. This along with high inotropic usage in the restrictive group limits study power and generalisation.
Some clarification would be useful. The CONSORT diagram should label the two study arms, where imbalance in numbers not receiving the allocated intervention (6/29 vs 1/29) may warrant further analysis. The proportion with invasive lines seems low, exact reasons for exclusion/non-inclusion could be detailed, and maximum age at enrolment given.
In our published RCT 2, three blood pressure (BP) intervention protocols were compared (BP below gestational age as in HIP, more active, or less active). This single centre pilot study randomised 60 infants <29 weeks, 45% of those screened and 100% of target recruitment, with invasive BP acquired every 10 seconds for a week. The HIP trial suggests their hypotension rate of 25% is low but without BP acquisition details, comparison is difficult. Their figure showing BP following dopamine or placebo requires data variability measures.
In our study, we found higher BP was associated with lower EEG discontinuity.3 The HIP study4 did not stipulate commonly used end-organ p...
We read with interest results from the Hypotension in Preterm Infants (HIP) trial by Dempsey et al.1 Unfortunately this multicentre randomised controlled trial (RCT) could not provide robust conclusions. Enrolment was limited to 58 of the planned 830 infants, 7% of those screened, attributed to strict inclusion criteria and recruitment challenges. This along with high inotropic usage in the restrictive group limits study power and generalisation.
Some clarification would be useful. The CONSORT diagram should label the two study arms, where imbalance in numbers not receiving the allocated intervention (6/29 vs 1/29) may warrant further analysis. The proportion with invasive lines seems low, exact reasons for exclusion/non-inclusion could be detailed, and maximum age at enrolment given.
In our published RCT 2, three blood pressure (BP) intervention protocols were compared (BP below gestational age as in HIP, more active, or less active). This single centre pilot study randomised 60 infants <29 weeks, 45% of those screened and 100% of target recruitment, with invasive BP acquired every 10 seconds for a week. The HIP trial suggests their hypotension rate of 25% is low but without BP acquisition details, comparison is difficult. Their figure showing BP following dopamine or placebo requires data variability measures.
In our study, we found higher BP was associated with lower EEG discontinuity.3 The HIP study4 did not stipulate commonly used end-organ perfusion tests;5 they found abnormal cranial ultrasound (CrUSS) in 50%, but with timing unclear. Our study found lowest CrUSS abnormality rates (21%) in the active arm.
We agree that RCTs examining neonatal haemodynamics are difficult, particularly consenting parents during challenging times. None of our parents gave antenatal assent, preferring postnatal consent. Simple designs with safety-netting (echocardiography and other non-invasive measures) to detect cardiovascular compromise encourage parental and physician participation and should be considered for future trials.
References
1. Dempsey EM, Barrington KJ, Marlow N, et al. Hypotension in Preterm Infants (HIP) randomised trial. Arch Dis Chid Fetal Neonatal Ed 2021 doi: 10.1136/archdischild-2020-320241
2. Pereira SS, Sinha AK, Morris JK, et al. Blood pressure intervention levels in preterm infants: pilot randomised trial. Arch Dis Child Fetal Neonatal Ed 2018 doi: 10.1136/archdischild-2017-314159
3. Pereira SS, Kempley ST, Wertheim DF, et al. Investigation of EEG Activity Compared with Mean Arterial Blood Pressure in Extremely Preterm Infants. Frontiers in Neurology 2018;9 doi: 10.3389/fneur.2018.00087
4. Dempsey EM, Barrington KJ, Marlow N, et al. Management of hypotension in preterm infants (The HIP Trial): a randomised controlled trial of hypotension management in extremely low gestational age newborns. Neonatology 2014;105(4):275-81. doi: 10.1159/000357553
5. Stranak Z, Semberova J, Barrington K, et al. International survey on diagnosis and management of hypotension in extremely preterm babies. European journal of pediatrics 2014;173(6):793-8. doi: 10.1007/s00431-013-2251-9
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
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.
2. Gray KD, Dudash K, Escobar C, et al. Prevalence and safety of diazoxide in the neonatal intensive care unit. J Perinatol 2018; 38: 1496-502.
Dear Sir or Madam!
Nasal CPAP is one of the most important therapies in neonatology. Accordingly, the manufacturers of such devices are very interested in gaining market share. Not all of their "sales arguments" correspond to clinical or physical reality. This is why studies comparing different devices are so extremely important.
The authors claim to have compared three CPAP systems that are referred to as "variable-flow" devices. This refers to CPAP systems that generate their CPAP through one or more jets, corresponding to jet ventilation as it is known in laryngeal surgery. But does the Miniflow CPAP belong in this category? The Miniflow has one inspiratory and one expiratory tube and does not have a jet. Pressure is generated through the expiratory valve of a ventilator. Such CPAP devices are actually called "constant-flow" devices.
Basically, the division into variable-flow and constant-flow devices is considered very confusing and, above all, physically questionable. However, the terms are very persistent. In any case, however, the statement of the study could be supplemented. It shows not only that there is no difference between variable flow devices, but equally no difference between variable and constant flow devices.
Yours sincerely,
Martin Wald
Ravaldi et al. in their letter raise two points of dispute. The first is linked to epidemiological data and the other to the fact that, according to them, a reduction in gynecological checks during pregnancy did not occur in the lockdown of spring 2020. I appreciate their engagement with the article but I disagree.
On the first point (epidemiological data), the difference between the data presented by Ravaldi and those indicated by us is linked to the fact that they mistakenly refer to older years. Ravaldi’s 2019 stillbirth is taken from the Italian Statistical Yearbook 2019, which refers to the entire 2016. Our data, obtained from the CEDAP (hospital discharge database, which records perinatal information on all newborns), are instead those of Mar-May 2019 and Mar-May 2020 (3 months of lockdown).
Furthermore, Ravaldi’s stillbirth data starting from 22 weeks were taken from the ISTAT Reproductive Health document published in 2018, which refers to 2015 data. The authors therefore cannot contest the difference in the results because they are using different data sources. A further analysis (to be published) on larger samples on all births in Lazio confirmed a significant difference between stillbirths in the period March-May 2020 compared to the same months in the years 2017-2019 (3.23 vs 1.83 per thousand, p value = 0.014) . The increase in stillbirths in the first half of 2020 was observed in numerous developed and developing countries as well as in Italy (1-...
Ravaldi et al. in their letter raise two points of dispute. The first is linked to epidemiological data and the other to the fact that, according to them, a reduction in gynecological checks during pregnancy did not occur in the lockdown of spring 2020. I appreciate their engagement with the article but I disagree.
On the first point (epidemiological data), the difference between the data presented by Ravaldi and those indicated by us is linked to the fact that they mistakenly refer to older years. Ravaldi’s 2019 stillbirth is taken from the Italian Statistical Yearbook 2019, which refers to the entire 2016. Our data, obtained from the CEDAP (hospital discharge database, which records perinatal information on all newborns), are instead those of Mar-May 2019 and Mar-May 2020 (3 months of lockdown).
Furthermore, Ravaldi’s stillbirth data starting from 22 weeks were taken from the ISTAT Reproductive Health document published in 2018, which refers to 2015 data. The authors therefore cannot contest the difference in the results because they are using different data sources. A further analysis (to be published) on larger samples on all births in Lazio confirmed a significant difference between stillbirths in the period March-May 2020 compared to the same months in the years 2017-2019 (3.23 vs 1.83 per thousand, p value = 0.014) . The increase in stillbirths in the first half of 2020 was observed in numerous developed and developing countries as well as in Italy (1-5).
On the second point, we had not indicated the precise causes of the increase in stillbirths as we did not have the data, but the most probable cause is the postponement of many medical checks that have affected all ages of life. It is true that all mothers love their children, but undoubtedly there has been a reduction in compulsory pediatric vaccinations and a postponement of many checks for fear of contracting coronavirus infection by going to hospitals and medical centers. For example, there was a reduction in emergency room activities and consequent delay in the diagnosis of various diseases, including serious ones (6-8). In the published article we never intended to blame women but we limited ourselves to observing a phenomenon.
In addition, in the study from Ravaldi et. al (9-10), the authors use a very limited sample and as they are aware there is also the risk of a sample selection bias: “Women likely to respond may have been better connected to health care and may have better access to internet and electronic facilities”.
Mario De Curtis, Leonardo Villani, Arianna Polo
References
1.Dell'Utri C, Manzoni E, Cipriani S et al. Effects of SARS Cov-2 epidemic on the obstetrical and gynecological emergency service accesses. What happened and what shall we expect now? Eur J Obstet Gynecol Reprod Biol .2020 Nov;254:64-68 July 10, 2020
2.A Khalil, von Dadelszen P, Draycott Tet al. Change in the Incidence of Stillbirth and Preterm Delivery During the COVID-19 Pandemic
3.Watson C. Stillbirth rate rises during coronavirus pandemic. Nature 2020, 585: 490
4.Mor M, Kugler N, Jauniaux E et al. Impact of the Covid-19 pandemic on excess perinatal mortality and morbidity in Israel. Am J Perinatol.2020 Dec 10, doi: 10.1055/s-0040-1721515
5. Kumari V, Mehta K, Choudhary R. Covid-19 outbreak and decreased hospitalisation of pregnant women in labour Lancet Glob Health 2020 Sep; 8(9): e1116-e1117. doi: 10.1016/S2214-109X(20)30319-3
6. Ciacchini B, Tonioli F, Marciano C et al., Reluctance to seek pediatric care during the COVID-19 pandemic and the risks of delayed diagnosis, in J. Pediatr., 2020 Jun, 29; 46(1):87, doi: 10.1186/s13052-020-00849-w;
7. Dopfer C, Wetzke M, Zychlinsky Scharff A et al., COVID-19 related reduction in pediatric emergency healthcare utilization – a concerning trend, in BMC Pediatr., 2020 Sep 7; 20(1):427, doi:10.1186/s12887-020-02303-6;
8. Lynn R. M, L Avis JL, Lenton S et al., Delayed access to care and late presentations in children during the COVID-19 pandemic: a snapshot survey of 4075 paediatricians in the UK and Ireland, in BMJ Arch. Dis. Child., 2020 Jun 25, doi: 10.1136/archdischild-2020-319848.
9. Ravaldi C, Vannacci A, The COVID-ASSESS dataset - COVID19 related anxiety and stress in prEgnancy, poSt-partum and breaStfeeding during lockdown in Italy. Data in Brief 2020 33, 106440 https://doi.org/10.1016/j.dib.2020.106440
10. Ravaldi C, Wilson A, Ricca V, Homer C, Vannacci A, Pregnant women voice their concerns and birth expectations during the COVID-19 pandemic in Italy, Women Birth (2020), doi: 10.1016/j.wombi.2020.07.002
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 MoreIn response to: "Early lung ultrasound affords little to the prediction of bronchopulmonary dysplasia".
We read with great interest the article by Dr Woods et al (1) that adds evidence to recent, large multicenter studies on lung ultrasound (LUS) as a predictive tool for bronchopulmonary dysplasia (BPD) (2-4). These studies, performed on a total of more than 600 infants, stem from a validated scoring system whose signs represent a progressive decrease in lung aeration in standardized ultrasound views (5). Notably, this approach is also well established in adult critical care (6).
Show MoreThe grading system adopted by Dr Woods and coworkers, has not been validated and its highest scores do not correspond to less air in the lung and therefore to a more severe pulmonary disease. Also, rather than the conventional sum of scores, Dr Woods et al. calculate a two-decimals mean score that may undermine the technique discrimination. None of these choices have ever been made for any other LUS scores, neither in neonates nor in older patients, despite ultrasound semiology and statistics needed to evaluate the predictive power are always the same (6). These factors may undermine the LUS prediction power for BPD.
Moreover, the authors needed a full ROC procedure to perform a formal diagnostic accuracy analysis, but even then, its strength would have been questionable with only 7 out 96 infants suffering from moderate-to-severe BPD (7) as target condition. This smal...
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]...
A reply to:
“Parenteral nutrition for preterm infants: Correcting for arachidonic and
docosahexaenoic acid may not suffice” by Bernard et al. regarding the publication:
Frazer LC, Martin CR. Parenteral lipid emulsions in the preterm infant: current issues
and controversies. Arch Dis Child Fetal Neonatal Ed. 2021 Jan 29: fetalneonatal-
2020-319108. doi: 10.1136/archdischild-2020-319108. Epub ahead of print. PMID:
33514630.
Lauren C. Frazer1,2, Camilia R. Martin2,3,4
1Division of Newborn Medicine, Boston Children’s Hospital, Boston, MA, USA
2Department of Pediatrics, Harvard Medical School, Boston, MA, USA
3Division of Translational Research, Beth Israel Deaconess Medical Center, Boston, MA, USA 4Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, MA, USA
Correspondence: cmartin1@bidmc.harvard.edu
Word Count: 216
Keywords: arachidonic acid, docosahexaenoic acid, lipid emulsions, preterm infant
Dear Editor,
We would like to thank Bernhard and colleagues for their thoughtful letter “Parenteral nutrition for preterm infants: Correcting for arachidonic and docosahexaenoic acid may not suffice” written in response to our review. The authors of the letter raised important issues regarding the lack of data surrounding the optimal balance of arachidonic (ARA) and docosahexaenoic acid (DHA) that should be administered...
Show MoreDear 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...
We read with interest results from the Hypotension in Preterm Infants (HIP) trial by Dempsey et al.1 Unfortunately this multicentre randomised controlled trial (RCT) could not provide robust conclusions. Enrolment was limited to 58 of the planned 830 infants, 7% of those screened, attributed to strict inclusion criteria and recruitment challenges. This along with high inotropic usage in the restrictive group limits study power and generalisation.
Show MoreSome clarification would be useful. The CONSORT diagram should label the two study arms, where imbalance in numbers not receiving the allocated intervention (6/29 vs 1/29) may warrant further analysis. The proportion with invasive lines seems low, exact reasons for exclusion/non-inclusion could be detailed, and maximum age at enrolment given.
In our published RCT 2, three blood pressure (BP) intervention protocols were compared (BP below gestational age as in HIP, more active, or less active). This single centre pilot study randomised 60 infants <29 weeks, 45% of those screened and 100% of target recruitment, with invasive BP acquired every 10 seconds for a week. The HIP trial suggests their hypotension rate of 25% is low but without BP acquisition details, comparison is difficult. Their figure showing BP following dopamine or placebo requires data variability measures.
In our study, we found higher BP was associated with lower EEG discontinuity.3 The HIP study4 did not stipulate commonly used end-organ p...
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...
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 Sir or Madam!
Nasal CPAP is one of the most important therapies in neonatology. Accordingly, the manufacturers of such devices are very interested in gaining market share. Not all of their "sales arguments" correspond to clinical or physical reality. This is why studies comparing different devices are so extremely important.
The authors claim to have compared three CPAP systems that are referred to as "variable-flow" devices. This refers to CPAP systems that generate their CPAP through one or more jets, corresponding to jet ventilation as it is known in laryngeal surgery. But does the Miniflow CPAP belong in this category? The Miniflow has one inspiratory and one expiratory tube and does not have a jet. Pressure is generated through the expiratory valve of a ventilator. Such CPAP devices are actually called "constant-flow" devices.
Basically, the division into variable-flow and constant-flow devices is considered very confusing and, above all, physically questionable. However, the terms are very persistent. In any case, however, the statement of the study could be supplemented. It shows not only that there is no difference between variable flow devices, but equally no difference between variable and constant flow devices.
Yours sincerely,
Martin Wald
Ravaldi et al. in their letter raise two points of dispute. The first is linked to epidemiological data and the other to the fact that, according to them, a reduction in gynecological checks during pregnancy did not occur in the lockdown of spring 2020. I appreciate their engagement with the article but I disagree.
On the first point (epidemiological data), the difference between the data presented by Ravaldi and those indicated by us is linked to the fact that they mistakenly refer to older years. Ravaldi’s 2019 stillbirth is taken from the Italian Statistical Yearbook 2019, which refers to the entire 2016. Our data, obtained from the CEDAP (hospital discharge database, which records perinatal information on all newborns), are instead those of Mar-May 2019 and Mar-May 2020 (3 months of lockdown).
Show MoreFurthermore, Ravaldi’s stillbirth data starting from 22 weeks were taken from the ISTAT Reproductive Health document published in 2018, which refers to 2015 data. The authors therefore cannot contest the difference in the results because they are using different data sources. A further analysis (to be published) on larger samples on all births in Lazio confirmed a significant difference between stillbirths in the period March-May 2020 compared to the same months in the years 2017-2019 (3.23 vs 1.83 per thousand, p value = 0.014) . The increase in stillbirths in the first half of 2020 was observed in numerous developed and developing countries as well as in Italy (1-...
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