663 e-Letters

  • 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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  • Response to comments of Dr Hutchon

    We would like to thank Dr. Hutchon for his considered letter and for highlighting a number of important points. We very much acknowledge his experience in the area of cord management at the time of delivery and his ongoing endeavours to advocate for appropriate cord management at the time of delivery(1). He correctly notes that there is no current formal policy for cord management at delivery for term newborn infants in our institution, which undoubtedly results in variability in practice. In a recently completed prospective study evaluating cardiac output in healthy term infants, we have noted that approximately one third of infants had early cord clamping and two thirds some form of placental transfusion, either as delayed or milking. Whilst we cannot be certain or draw any definitive inferences, it is likely that this same variability exits in our cohort of patients. The point related to ‘immediate transfer’ to the resuscitaire may be somewhat misleading. This    relates to once the cord is clamped, and not that the cord was immediately clamped in each case(2).  We acknowledge that this terminology may be confusing, and therefore cannot concur that our results relate to early cord clamping alone. It is also important to highlight that all our newborns were spontaneously breathing at delivery and did not require any assistance with adaptation.

    He makes a very valid comparison with oxygen saturation values in term infants highlighti...

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  • Prediction of bronchopulmonary dysplasia

    To the editor;
    We have read the study of Hunt et al. describing the prediction of bronchopulmonary dysplasia (BPD) development at 1 week of age. (1). As it is very well known, BPD is a multifactorial disease with different clinical forms such as mild, moderate and severe. Early prediction of the disease is a clinically significant issue, such that early preventive measures may be taken, especially in cases with high risk. In our opinion, basing the prediction of BPD only on the ventilation requirement at 1 week of age is not appropriate. Respiratory distress syndrome and mechanical ventilation are important factors in the development of BPD but mechanical ventilation need is not sufficent enough for prediction in a disease with many risk factors. We had developed a simple clinical scoring system for the prediction of BPD, which takes into account the birthweight, gestational age, gender, hemodynamically signifiicant patent ductus arteriosus (HsPDA), respiratory distress syndrome, hypotension and intraventricular hemorrhage, at 72 hours of postnatal age (2). A score of less than 4 was considered as low, 4-6 as low intermediate, 7-9 as high intermediate and a score of above 9 was considered as high risk, in order to optimize the predictive values of lowest and highest categories. Among these parameters, HsPDA was the most significant one. The receiver operator curves (ROC) was 0.930, the negative predictive value of a score less than 4 were 95,9 whereas a positive pre...

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  • Nebulised Surfactant Therapy : Needs Rigorous pragmatic Trial before Implementation

    We read with great interest the article by Minocchieri et al., published in this journal and found it very interesting and relevant to the current context.1 However, we have certain observations about the conduct of the study which question its external validity.
    The authors used supplemental fractional inspired oxygen (FiO2) of 0.22–0.30 as enrollment criteria for administering surfactant. As per current standard, most of the neonatologist will not agree to give surfactant at such a low FiO2 requirement in the first 4 hours. It might be possible that many enrolled babies could have been easily managed without surfactant and it was an unnecessary intervention for them. This is further supported by the fact that in current study 28% of babies were weaned to room air in the first 4 hours, hence could not be enrolled. Also, the author's suggestion of enrolling babies requiring Fio2 > 25 % seems to be very liberal. Most of the units administer surfactant beyond 30% supplemental oxygen requirement.
    The total duration of invasive as well as any mechanical ventilation was higher in the intervention group, suggesting that the harms may outweigh the benefits.
    Although the authors showed that the intervention had its intended effect in babies born at >32 weeks’ gestation, in the current era, where universal antenatal steroid coverage is available, these babies hardly need surfactant. In this trial, a significant number of babies > 32 weeks received su...

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  • End-expiratory pressure during the respiratory transition: a more complex tale?

    I agree with the authors that the question of end-expiratory pressure at birth needs to focus on CPAP. As the authors highlight, the entirety of the preclinical literature has been performed in mechanically ventilated, intubated and sedated animals, and the role of PEEP on pulmonary blood flow during the actual respiratory transition is yet to be investigated. Neither of these limitations are insurmountable and I am confident the authors can rectify this gap in knowledge.
    The rapidly changing cardiorespiratory events immediately following birth and the concerns regarding with too low and too high a PEEP further emphasise the need for a dynamic approach to PEEP levels.

  • Response to the letter to the editor by Zhu et al regarding “Non-invasive high-frequency oscillatory ventilation in preterm infants”

    Dear Editor

    We appreciate the comments of Zhu and Shi on our crossover trial comparing nHFOV (nasal high frequency oscillatory ventilation) and nCPAP (nasal continuous positive airway pressure) in preterm infants <32 weeks gestational age after extubation from invasive ventilation for respiratory distress syndrome or after less invasive surfactant therapy.1

    The aim of our study was to evaluate the efficacy of an oscillatory pressure waveform superposed to CPAP in spontaneously breathing preterm infants suffering from hypercarbia. In our trial, patients received a CPAP of 5 – 8 cmH2O, which represents standard of care in our unit and is in line with the clinical practice within many neonatal centers.2 Individual CPAP levels were the same before (adjusted according to standard of care) and within the study periods.
    We agree with Zhu et al that increasing the CPAP level in addition to oscillations may enhance lung recruitment and ventilation. However, the effect of oscillations can hardly be differentiated from elevated CPAP levels in this scenario. Other factors than increased lung recruitment might contribute to increased CO2 clearance (e.g. increased leak flow, increased pharyngeal washout or the infants’ respiratory response). In conclusion, we cannot speculate on the effect of increased CPAP levels when testing nHFOV in our trial, but we would advise against testing differing opening pressures when comparing nHFOV to CPAP respiratory support.

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  • The secret sauce: one ingredient

    Response to The secret sauce: secrets of high performing neonatal intensive care units
    Soghier and Short highlight the importance of local contextual factors in determining the success of improvement initiatives in neonatal units. They draw attention to a number of qualitatively assessed factors, many of which are prefixed by the adjectives “effective”, “active” and, “strong” reflecting the importance of leadership and team culture in effective organisations.

    Whilst contextual factor surveys might have a place in identifying the readiness of teams to undertake active improvement, they do little to assist organisations in improving their own readiness. The features of good healthcare leadership and team culture are not readily measured, and healthcare professionals in the UK have little or no training in the attitudes and skills necessary for leadership in quality improvement.

    The Institute for Healthcare Improvement has attempted to describe the features of a high quality healthcare organisation in some detail (1). The British Association of Perinatal Medicine has recently produced Quality Indicators relating to structures and processes relevant to Quality and Patient Safety in the context of current neonatal care in the UK (2), which it is hoped will create a basis for units to develop “quality-readiness”.

    There is reason to believe that collaboration across centres might add momentum to quality improvement (3). The UK, which has good access to...

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  • Respiratory adaptation in term infants following elective caesarean section and early cord clamping ?

    Finn et al (1) describe respiratory adaptation in term infants following elective caesarean section and the other intervention of early cord clamping(2). Although the timing of cord clamping was not documented and there is no policy for delayed cord clamping at Cork University Maternity Hospital, the authors state that the neonates were transferred immediately after birth to a Panda Resuscitator and other non-invasive monitoring equipment, thus requiring early cord clamping in all infants studied.

    The aim of the study was to define newborn physiological ventilation parameters (respiratory rate (RR), TV, end-tidal carbon dioxide (EtCO2)) over the first minutes of life in healthy-term infants following ECS, in the same way that Dawson and colleagues(3) produced centile charts in 2010 detailing the normalisation of oxygen saturations over time during newborn adaptation after normal vaginal birth. All the babies studied by Dawson et al also experienced a transition of the circulatory system which was interrupted by early cord clamping but, in a study in 2014 by Smit et al(4), in which cord clamping was delayed by at least one minute, they showed that cord clamping had resulted in a lower oxygen saturation during the first few minutes after birth. The median SpO2 of the babies experiencing early cord clamping was 11, 7 and 4% lower at minute 1, 2 and 3 respectively. All these babies already had the advantage of a physiological preparation through the mechanical and hor...

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