81 e-Letters

published between 2016 and 2019

  • Sepsis and neurodevelopmental outcome in preterm neonates

    In their follow-up analysis of the PREMILOC trial, Baud et al.[1] found significantly better neurodevelopmental outcomes at 22 months postmenstrual age in those extreme preterm neonates of 24 and 25 weeks of gestation who had been treated with early hydrocortisone during the first ten days after birth. Improvements in global neurological assessments were most pronounced for moderate to severe neurodevelopmental impairment, with a prevalence of 2.1% in the hydrocortisone and 18.4% in the placebo group. In this context it has to be remembered that early hydrocortisone treatment had been associated with a significant increase in the late-onset sepsis rate before discharge for those most immature neonates of 24 and 25 weeks of gestation.[2]
    In their meta-analysis including seventeen observational studies, Alshaikh et al.[3] described “an increased risk of one or more long-term neurodevelopmental impairments … including cerebral palsy” in very-low-birth-weight infants who had suffered from culture-proven sepsis during the neonatal period. A follow-up analysis of extreme preterm neonates below 32 weeks of gestation found a significantly higher frequency of cerebral palsy at five years of age in those who had developed early- and/or late-onset sepsis.[4] Correspondingly, a positive association of Coagulase-negative staphylococcus sepsis and the risk of cognitive delay at a corrected age between 30 and 42 months has been reported in preterm neonates below 29 weeks of gestati...

    Show More
  • The value of C-Reactive Protein in treatment decisions for early onset neonatal sepsis

    Dear Editor
    We read with interest the letter by Sur et al in response to our article (1). It was very reassuring to note that our findings were replicated in their study confirming the potential scale of antibiotic reduction while identifying all ‘blood culture positive’ sepsis. We did not collect data on CRP in our study. The evidence does not support a single CRP measurement as a reliable tool to help decisions to initiate treatment in the context of early onset neonatal sepsis (EOS), particularly in asymptomatic infants[2]. Consistent normal values over first 48 hours are associated with absence of EOS; but abnormal values in an asymptomatic infant are unreliable to predict culture proven sepsis [2-5]. CRP concentrations increase in neonates in response to a number of non-infective inflammatory conditions such as asphyxia, meconium aspiration, tissue trauma and pneumothorax. Serial CRP trend is irrelevant in treatment initiation decisions, and in low incidence conditions such as EOS, its value in predicting true culture positive EOS is below that is expected of a good and reliable test (Likelihood ratio 3.0)[4,6). The American Academy of Paediatrics states that diagnosis of EOS cannot be made using CRP in the absence of positive blood or CSF culture [2]. For asymptomatic low / moderate risk infants (currently treated with presumptive antibiotics), a period of observation / serial physical examination may be used instead of invasive tests to identify at an early...

    Show More
  • Target range 90-95% vs. 91-95%

    We were impressed by the conduct and results of Reynolds et al.’s randomised controlled cross-over trial comparing Vapotherm’s IntellO2 device with manual control of inspired oxygen, showing improvement in the proportion of time spent within the target oxygen saturation range (automated arm mean 80% of time in 90-95% range vs. manual 49%). The findings are consistent with a meta-analysis referenced within their paper [1].

    The Neonatal Oxygenation Prospective Meta-analysis (NeOProM) shows that targeting oxygen saturations of 91–95% with an oximeter with a correctly configured algorithm, carries a 38% survival advantage [2]. The co-ordinator of the NeOProM collaboration has stated that the “Infants born extremely preterm … should have their oxygen saturation levels targeted between 91% and 95%” [3].

    The difference between the saturation targeting approach adopted by Reynolds et al., and NeOProM may appear small but, on account of the sigmoidal shape of the haemoglobin–oxygen dissociation curve, significant hypoxic shifts will occur with small changes in oxygen saturation.

    Given the rigor of the NeOProM findings, would Reynolds et al. agree that targeting oxygen saturations of 91-95% is an important first step, whilst we wait for products which will allow improved titration of oxygen delivery?

    [1] Mitra S, Singh B, El-Naggar W, McMillan DD. Automated versus manual control of inspired oxygen to target oxygen saturation in prete...

    Show More
  • Not necessarily aortic perofration

    Thank you for an interesting case but the position of the arterial catheter after the perforation suggests to me that this was from an umbilical artery rather than the aorta (compare the path on the abdominal wall on the 2 x-rays).

    This may therefore be why you were able to successfully manage this conservatively.

  • Thrombosis after umbilical venous catheterisation

    We kindly thank Da Lozzo et al. for their reaction to our paper. Indeed, many variables may be of influence on the incidence of thrombosis in our study group.
    The authors are correct that the incidence of necrotizing enterocolitis in our study group (12.5%, 5/40) is higher than expected based on literature. As shown by Battersby et al. comparing NEC incidences internationally is challenging (1). The incidence of NEC in our study group does not reflect the NEC incidence of last 15 years at our department (which was 3.7% (98/2626) in infants with a gestational age <32 weeks). Possibly, the higher incidence of NEC led to a higher incidence of thrombosis in our study. However, care should be taken when interpreting our results due to the small sample size (n=40).
    Da Lozzo et al. make a valuable point about the diameter of central venous catheters. Most (25/40) umbilical venous catheters (UVCs) used in our study-group were 4Fr Vygon catheters, single or double lumen, with an external diameter of 1.5 and 1.4 mm, respectively (strange enough double lumen is smaller than single lumen). In 3/40 infants 5Fr Vygon catheters (external diameter 1.7 mm) were used and in 10/40 infants 3.5Fr Vygon catheters (external diameter 1.16 mm). In 2/40 infants the size of the catheter was not registered. We found no association between the risk of thrombosis and the size of the catheter (p=0.59). However, as stated in the discussion of our paper, the sample size of our group is too...

    Show More
  • Umbilical venous catheterisation and risk of thrombosis

    We appreciated the paper by Dubbink-Verheij et al. evaluating the incidence of thrombosis in newborns who underwent umbilical catheterization in comparison with a control group of infants without umbilical venous catheter (UVC). While the paper highlights specific issues about UVC-related thrombosis in NICU, regarding the sites, the time of onset and the outcomes of this condition, we suggest that some relevant variables have not been taken fully in account.
    Some of the comorbidity rates of the patients in the study group are not consistent with data from literature and might have had a role in the unusual high rate of thrombosis and poor outcome in the study group. The reported rates of necrotizing enterocolitis (NEC; 12.5% in the study group, 10% in the total population of the study) is significantly higher compared with that of the Vermont Oxford Network (VON); VLBW infants between 2000 and 2009 based on the VON showed a NEC incidence of 4.6-6.1%. (1)
    The study reported 30 thrombotic episodes in defined locations but, remarkably, the type and the diameter of catheter utilized was not stated by the Authors. Neonates, and especially preterm neonates, have an unfavorable catheter-to-vessel diameter ratio, which is a recognized risk factor for the development of catheter-related thrombosis in CVCs. In a in vitro model Nifong and McDevitt (2) quantified the impact of the catheter to vein size ratio on fluid flow unraveling the mechanism by which risk of catheter-...

    Show More
  • 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...

    Show More
  • 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...

    Show More
  • 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...

    Show More