710 e-Letters

  • Using the Kaiser -Permanente (KP) sepsis calculator to assess possible reduction in screening for early onset neonatal sepsis (EONS)- a prospective modelling study in the north-west

    We have read with great interest the article by Goel et al and found it very relevant. We have also been following keenly the reports from other units on successful implementation of the KP sepsis calculator in UK. Encouraged by the positive outcomes and increased use of the KP screening tool, 3 tertiary neonatal units in the NW,namely East Lancashire Hospital NHS Trust, Royal Bolton Hospital and Royal Preston Hospital decided to collect 3 months of prospective data of EONS screening and compare its recommendations against the existing practice based on CG149. All of the aforementioned units use specific CRP cut-offs to label and treat as presumed sepsis. Between the 3 units 313 babies were screened for EONS in the 3 months at a screening rate of 8.2%. Although the KP tool would have reduced screening by a significant 72.5% in average, the combined sensitivity and specificity were 50% and 82% respectively. The KP identified all true "blood-culture positive" sepsis but a large number of babies whom the KP would not have recommended screening or observation mounted high CRP responses and ended up getting treated with antibiotics. Now none of these babies were clinically unwell or grew positive blood or CSF cultures. Hence it will be interesting to see whether maternal factors like fever or pre-eclampsia resulted in this high CRP response. It also reflects the lack of accuracy of CRP and flaw in CRP based approach. It is also worth considering whether baseline di...

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  • Caution in extrapolating results to first two weeks of life

    I was interested to read this study looking at a question which is extremely important to mothers of preterm infants who need to exclusively express - "how frequently do I need to express?".

    The conclusion that there is no difference in average yield of mothers expressing 5, 6, 7, 8, and 9 times a day will be very useful to mothers who are similar to those included in the study - that is mothers of preterm babies aged at least 10 days (but mostly 15-20 days old), who have good daily expressed milk yield (average yield clustered around 750ml/day for these expressing frequencies). Therefore mothers in this group may feel more confident in reducing their expressing sessions down to a more manageable 5 or 6 per day, which reduces their burden of expressing.

    However it could be harmful to extrapolate outside of these characteristics, for example mothers attempting to establish their supply in the first 2 weeks of life. We know that this period may be a critical window to establish milk supply and this study cannot comment on the relationship of early expressing frequency to the establishment of adequate yield (which, to complicate matters further, is poorly defined in the context of prematurity, with a range of daily volume targets from 500-900ml suggested in the literature and by the Unicef Baby Friendly Initiative). Already I have seen the article summarised as "mothers of preterm infants should express milk at least 5 times a day" on social...

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  • Dr Ilana Levene

    Thank you for this interesting article, which really adds to our understanding of management of neonatal hypoglycaemia. However, your conclusion that a subset of babies should receive formula rather than breastfeed alongside gel, depending on their blood glucose level, is not supported by the evidence you have provided and ignores the potential harm associated with this approach.

    Your data states that alongside the first use of gel, breastfed babies are more likely to require a second gel. There is no literature to support the idea that experiencing a second transient hypoglycaemia in a carefully monitored baby in the first 48 hours of life is harmful (indeed UK guidance uses a treatment threshold of 2mmol/l for the entire first 48 hours of life), and alongside the second gel breastfeeding is as effective as formula so there is no reason to suppose from the data provided that breastfed babies are more likely to go on to require intravenous dextrose.

    Asking breastfeeding mothers to use formula instead of breastfeeding in the first hours of their baby's life is likely to undermine mothers' trust in breastfeeding, may impact on their milk supply through reduced stimulation in the critical time period and reduces the colostrum volume ingested, with its unique immune properties. It is not a recommendation to be made lightly.

  • UK neonatal resuscitation survey - a word of caution

    As authors of the 2015 guidelines we read with interest the “UK neonatal resuscitation survey” [1]. Comparison with 2012 shows a rewarding positive effect of successive guidelines on newborn resuscitation practice.

    However, we wanted to address this statement: “…updated guidelines have been criticised for failing to consider data from the Targeted Oxygen in the Resuscitation of Preterm Infants [To2rpido]”. To2rpido [2], published 2017, was unavailable for inclusion in 2015 ILCOR reviews of evidence. [3]. The analysis referred to was post-hoc and unprespecified. Clinicians were not blinded and recruitment was problematic. Enrolling only 5% of eligible infants, To2rpido was terminated after reaching 15% of targeted sample size due to loss of equipoise: ironically, clinicians were concerned about using high oxygen concentrations.

    Nonetheless, To2rpido generated such interest that it led to the first neonatal review in ILCOR’s continuous evidence evaluation strategy. [4] Utilising GRADE methodology to rate quality of evidence and strength of recommendations, To2rpido’s impact was downgraded because of high risk of bias. This review [4] continues to recommend “starting with a lower oxygen concentration (21–30%) compared to higher oxygen concentration (60–100%)” whilst highlighting many gaps in our current knowledge.

    The use of end-tidal CO2 (ETCO2) detection was not recommended because the guidelines, and Newborn Life Support (NLS) course, focus on airwa...

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  • Methodology concerns about a network meta-analysis

    Dear Editor,
    We read with great interest the network meta-analysis performed by Zeng et al [1]. The authors investigated the comparative efficacy and safety of different corticosteroids in the prevention of bronchopulmonary dysplasia in preterm infants. They included 47 RCTs with 6747 participants. We have several concerns about the study.
    First, it looks that the authors are unfamiliar with the procedures of network meta-analysis because there were obvious mistakes. Figure 1 in the study was network plot of different corticosteroids. In Figure 1, the circle size should be proportional to the sample size randomised to each intervention [2]. The line width should be proportional to the study numbers of each direct comparison. However, the circle size was not proportional to the sample size in Figure 1. The line width between dexamethasone (high dose) and placebo also seems inadequate.
    Second, various statistical methods or plots have been suggested to assist interpreting the results of network meta-analysis [3]. However, many of them were not performed or presented in this study. For example, since there were direct estimates (i.e., results of pairwise meta-analysis) and indirect estimates (i.e., results of network meta-analysis), the inconsistency between them should be assessed and explored because important inconsistency could threaten the validity of the results. Besides, the authors also didn’t assess small-study effects. Small-study effects could mat...

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  • Impact of delivered tidal volume on the occurrence of intraventricular haemorrhage in preterm infants during positive pressure ventilation in the delivery room

    There seems to be a descrepency regarding the number of babies intubatec in two groups. 56 babies were intubated in high tidal volume group against 14 intubated in the low tidal volume group as per the article. I wondering whether it might have contributed to the high incidence of IVH in the high tidal volume group.

  • Delivery of positive end-expiratory pressure to preterm lambs using common resuscitation devices

    I congratulate Dr Thio and colleagues on their study of PEEP delivery in common neonatal resuscitation devices. This study is timely as clinicians look for more refined strategies to support the preterm lung at birth. Such strategies will require a reliance on equipment in the delivery room.
    To allow for interpretation of the findings into the clinical context could the authors comment on the number, and characteristics, of lambs studied, and was this accounted for analysis in Table 1 (for example cluster analysis)? What was the pressure of medical gas supply?

  • Impact of human milk on bronchopulmonary dysplasia-Reply

    In Reply

    We would like to thank Miller et al for their interest in our recently published review and their responding letter to the editor. The first concern is combining RCTs and cohort studies. We agree that classic Cochrane methods advocate combining only same study designs in a meta-analysis. However, there is also an alternative viewpoint. Appropriate integration of randomized and observational cohort studies may offer opportunities to provide more timely, comprehensive, and generalizable evidence about the medical intervention1. To date, the majority of human milk studies on bronchopulmonary dysplasia (BPD) have been observational cohort studies. Generalizing extensive perspective is motivation for combining randomized and non-randomized evidence in a meta-analysis2. In our review, to detect the possibility of incorporating randomized and observational cohort studies, we assessed the statistic heterogeneity between cohort studies and randomized studies. The test for subgroup differences has been shown in table 3, which demonstrated the statistic heterogeneity (I2 and P values) is generally low. This gave a plausible reason to pool observational and randomized studies in our review. In fact, combining observational and randomized studies has been also performed in a similarly themed review for preventing BPD, when authors compared raw mother’s own milk with pasteurized mother’s own milk3.

    The second concern from Miller et al was how to interpret the out...

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  • Response to comments of Dr Fahri Ovalı

    We thank Ovali et al for their interest in our paper. They emphasise that BPD results from a multifactorial process and has wide variation in severity. We agree that basing the prediction of BPD solely on ventilatory requirement at one week of age would not identify all cases of BPD, as demonstrated by the low sensitivity of 67% demonstrated in our study.[1] The high sensitivity of ventilation at one week of age in predicting the development of BPD (99%), however, means that it could facilitate counselling of parents and act as a screening tool to identify candidates for future trials of therapeutic interventions to prevent BPD.

    [1] Hunt K, Dassios T, Ali K, et al. Prediction of bronchopulmonary dysplasia development. Arch Dis Child Fetal Neonatal Ed 2018 [Epub ahead of print].

  • Validity and relevance of outcomes; the importance of core outcome sets

    I wish to comment about the outcomes you have selected for your study on gastroschisis and in particular caution against the use of 'primary closure' as an outcome at all. There are a number of reasons for this. Firstly, implicit in the use of primary closure as an outcome is a belief that it is either a good or bad thing. The literature would not support that either delayed closure or primary closure is superior, therefore it is impossible to know how to interpret a higher (or lower) rate of primary closure following either Caesarian section or vaginal delivery. Is a higher rate of primary closure good or bad? Secondly, the increasing use by paediatric surgeons of the preformed silo to manage return of the visceral contents to the abdominal cavity means that the closure technique may be prescribed rather than one that is dependent on other factors (such as mode of delivery). Its relevance therefore as an outcome is highly questionable.

    I note also that you encountered 'differences in definition of outcomes, choice of outcome measures and variation in reporting methods'. Such difficulties can be a real challenge in the context of a meta-analysis and preclude accurate evidence synthesis. One proposed way to address this challenge is the development and use of a Core Outcome Set. A Core Outcome Set is a set of outcomes that has been derived through consensus methodology across stakeholder groups as being the most important outcomes to measure in re...

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