704 e-Letters

  • Low dose Diazoxide for Hyper-insulinemic hypoglycemia- Do we agree?

    We read with great interest this article published by Chandran et al. However, we have some critical
    reservations on implementation of low dose diazoxide. The target blood glucose thresholds used for
    management have been taken from Pediatric endocrine society guidelines of 2015, which are based
    on adult neuroglycopenic effects. However, AAP guidelines recommend a lower treatment target of
    <2.2 mmol/l (40 mg/dl) for asymptomatic,<2.5 mmol/l (45 mg/dl) for symptomatic neonates
    during first 48 hours and <3.3 mmol/l (60mg/dl) thereafter (1, 2) . Moreover, in a recent multi-centric
    trial published by Kempen et al; it was concluded that low treatment threshold of <2 mmol/l (36
    mg/dl) was non inferior in terms of neurodevelopmental outcomes at 18 months of age in healthy
    asymptomatic neonates (3) . Hence it is still debatable whether all the neonates being managed for
    hypoglycemia warranted an intravenous glucose infusion therapy and diazoxide.
    Authors have used a combination of starting dose of diazoxide along with hydrochlorothiazide for
    management of SGA neonates; which are known to have a synergistic effect on increasing blood
    glucose levels, hence actual dose of diazoxide required if used alone could have been potentially
    higher in these neonates.
    In the study design the authors have mentioned that this was an observational cohort study,
    however neither the absence of compar...

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  • Response to Comments on the analyses and the generalizability of findings from the Economic Evaluation of SIFT

    We thank the authors for the comments on the Economic Evaluation of SIFT (1) and we are grateful for the opportunity to respond to their comments.
    Taking each of the authors’ points in the order in which they are presented:
    1. In relation to the first point about the loss to follow up and the exclusion of such patients from the analysis, we point out that we used complete case analysis and accounted for the missing patients following best practice using a multiple imputation analysis which is provided in the supplementary materials. We state the following in the paper:

    “Mean total costs for all infants, adjusting for missing data using multiple imputation, are found in the online supplementary table S3. When the missing values were accounted for, faster feed increments remain more costly in comparison to slower feed increments but at a slightly higher level (£378 more) per infant, reflecting the high level of uncertainty in the difference in costs, especially with regard to the healthcare resource use after discharge estimated by the multiple imputation” (last paragraph of methods))

    2. In relation to the authors second concern, whilst death was slightly higher in the slower feeds arm during initial hospital stay there are two important points in response to this. First, we clarify that by definition economic analysis is not an exercise in accountancy where death is assumed to incur a zero cost, because economic evaluation focuses on costs and ou...

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  • Visual assessment after HIE

    Dear authors, dear editors,

    Thanks for this excellent focus on visual abilities of infants following HIE.
    More than three decades ago, at a time when brain imaging of newborns with HIE was limited to ultrasound and CT scanning, we have published impairments of visual functions at an early age (Early Hum Dev 1989;20:267-279 and Neuropediatrics 1990;21:76-78) .
    We could do so using standardized, outpatient methods of visual assessment.
    Further use of this relatively simple tools could and should be part of assessments of infants with HIE, in particular when (diffusion weighted) MRI indicates involvement of visual tracts.

    With kind regards,

    Floris Groenendaal

  • Response to Lack of data/evidence to back recommendations for significant change of practice

    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...

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  • The need for adequate methodology to study bronchopulmonary dysplasia using lung ultrasound

    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...

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  • Re: Neonatal videolaryngoscopy as a teaching aid

    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]...

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  • A reply to: “Parenteral nutrition for preterm infants: Correcting for arachidonic and docosahexaenoic acid may not suffice” by Bernard et al.

    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:

    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...

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  • Letter/Comments to Editor on paper “Necrotizing enterocolitis in newborns receiving Diazoxide” published in ADC Fetal Neonatal Ed 2020; 0: F1-F5.

    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...

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  • Blood pressure trials in preterm infants

    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...

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  • Is MRSOPA algorithm a cause for concern?

    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...

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