46 e-Letters

published between 2019 and 2022

  • Response to "How to Recognise encephalopathy earlier?"

    We have read with interest the response by Dr. Shabih Manzar on our article. The Thompson score is a clinical score consisting of nine items that are associated with neurologic dysfunction to assess the severity of neonatal encephalopathy (NE) in infants with perinatal asphyxia.[1] There are indeed important limitations that need to be considered; the assessment of infants by use of the Thompson score requires interpretation from the examiner, and the degree of NE may change over time.[2] It should be noted that these limitations are also applicable to other clinical grading tools, such as the modified Sarnat score, which is being widely applied to select infants for therapeutic hypothermia.[2,3] We would like to emphasize that the majority of the infants described in this study was born in a level-II-hospital. Amplitude-integrated electroencephalography (aEEG), another tool to select infants for therapeutic hypothermia, allows continuous monitoring, expert revision and the detection of subclinical seizures, but also requires well-trained staff for correct interpretation and is often not available in these hospitals. By design, the Thompson score did not require extensive training of the observer, which is why it is suitable to be used in smaller hospitals.[1] In a previous study, our study group demonstrated that the Thompson score and aEEG had a similar predictive value for an adverse outcome.[4] We however completely agree with Dr. Manzar that it is of concern that the...

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  • How to Recognise encephalopathy earlier?

    The article by Parmentier et al [1] highlights the role of Amplitude-integrated electroencephalography (aEEG) and early biomarkers in selecting infants for therapeutic hypothermia (TH). They also suggested the role of the Thompson score (TS) in asphyxiated infants. The problem with TS is that it is subjective. It consists of nine clinical signs: tone, level of consciousness, fits, posture, moro reflex, grasp, suck, respiration, and fontanelle, which could change over time [2]. Also, in the data presented by Parmentier et al [1], twenty-one (53%) infants did not have TS performed.

    It was surprising to note that four cases that had moderate neonatal encephalopathy (NE) were not treated with TH despite having seizures within the first 6 hours. The reason for not treatment was rapid recovery. What was the definition of rapid recovery? According to the published flow diagram for NE, the onset of seizure within 6 hours warrants TH [3].

    The definition of perinatal asphyxia used by Parmentier et al [1] was from a study in 2003 [4]. It was defined as an arterial cord blood pH <7.1, Apgar Score <7 at 5 min, or need for neonatal resuscitation. While the analysis was done with pH of < 7 and > 7 [(Table 1) 1]. A pH of 7.1 and Apgar of 7 at 5 min is higher than the definition/criteria used in the TH trial [5].


    1. Parmentier CEJ, Steggerda SJ, Weeke LC, Rijken M, De Vries LS, Groenendaal F. Outcome of non-cooled asphyxiated infants w...

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  • Therapeutic Hypothermia in Mild Hypoxic Ischemic Encephalopathy

    I agree with Yieh et al [1] that there is an overuse of therapeutic hypothermia (TH) in mild HIE resulting in increased resource utilization. The two main reasons we see this practice are the fear of litigation and scare that infant would later have neurological problems. DuPont et al [2] reported abnormal short-term neurologic outcomes in 20% of newborns with perinatal acidemia and mild HIE not treated with TH. However, in the same study they had 14% of infants that did not receive TH despite the neurological examination consistent with moderate and severe HIE.
    Mehta et al [3] have earlier described overutilization of TH in mild HIE, recommending a robust review of the eligibility criteria definitions, especially the 10-min Apgar score. The subjectivity of TH criteria put the practitioner in a decision dilemma. For example, out of five components of Apgar score, only heart rate assessment is objective. A color score of 1 or 2 can change the Apgar from 5 to 6. Similarly, a slight variation in observer examination in obtaining Sarnat score could change it from mild to moderate. Therefore, using a combination of factors in deciding about TH would be a better approach [4].
    One of the most important criterion for TH is presence of perinatal academia. Recently, Blecharczyk et al [5] have shown the benefits of standardized screening pathway for evaluating abnormal cord gases in neonates at risk for HIE. Following a structured pathway resulted in minimizing unnecess...

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  • Head Growth looking beyond the NICU

    In this study Selvanathan et al [1] showed small birth head circumference (HC) to be associated with poorer neurodevelopment outcome, independent of postnatal illness and white matter injury. They concluded that normalisation of HC during NICU care appears to moderate this risk.

    It was interesting to note that normal/small group had the highest chorioamnionitis (40%), lowest ROP (0) and highest NEC (30%) rates. They also received the highest Energy (kcal/kg/day), median 80. What could be the reason for the HC to regress from normal to small?

    We need to investigate other factors that affect the head growth. The individual factors such as parental bonding and availability, environmental exposure to noise, light and other stimuli may have some role in slowing the head growth.

    Interestingly, in the same issue of ADC, Ni et al [2] have shown poor HC growth in EPICure2 that was unchanged from EPICure, which is alarming.

    1. Selvanathan T, Guo T, Kwan E, et al. Head circumference, total cerebral volume and neurodevelopment in preterm neonates. Arch Dis Child Fetal Neonatal Ed. 2022;107(2):181-187. doi:10.1136/archdischild-2020-321397

    2. Ni Y, Lancaster R, Suonpera E, et al. Growth in extremely preterm children born in England in 1995 and 2006: the EPICure studies. Arch Dis Child Fetal Neonatal Ed. 2022;107(2):193-200. doi:10.1136/archdischild-2020-321107

  • Umbilical Venous Line Extravasation

    Kamupira et al [1] presented a case of umbilical venous line extravasation that was confirmed by contrast study. To justify the contrast use they stated, “There is evidence routine contrast use in checking tip positions improves long line positioning (reference 3 on the paper) and British Association of Perinatal Medicine (BAPM) has included this in it's central access guidance (reference 4 on the paper)”. The caveats with this statement are that first umbilical lines are not synonymous to long lines and second that in BAPM executive summary statement there is no mention of contrast use, “The findings of the Working Group recommend that:
    • Any clinical deterioration of a baby in whom a central venous catheter is present should raise the question of catheter-related complications, particularly infection, extravasation and tamponade.
    • All central catheter tips should be positioned outside the cardiac silhouette.
    • An umbilical venous catheter (UVC) tip should ideally be sited at T8-T9 (assuming this lies outside the cardiac silhouette). A UVC tip sited at or below T10 carries a significantly higher risk of extravasation. It may be necessary to use these catheters in the short term, but they should be replaced at the earliest opportunity”.
    In fact, the use of contrast has been associated with hypothyroidism in neonates [2]. UVC misplacements happen either due to the wrong placement or due to the migration of UVC from a safe to wrong position. Th...

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  • 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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