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.
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.
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?
References:
[1] Mitra S, Singh B, El-Naggar W, McMillan DD. Automated versus manual control of inspired oxygen to target oxygen saturation in prete...
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?
References:
[1] Mitra S, Singh B, El-Naggar W, McMillan DD. Automated versus manual control of inspired oxygen to target oxygen saturation in preterm infants: a systematic review and meta-analysis. Journal of Perinatology. 2018; 38, 351–360 doi:10.1038/s41372-017-0037-z
[2] Askie LM, Darlow BA, Finer N, et al. Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-Analysis Collaboration [published correction appears in JAMA. 2018 Jul 17;320(3):308]. JAMA. 2018;319(21):2190–2201. doi:10.1001/jama.2018.5725
[3] Askie LM., Meta-analysis of Oxygenation Saturation Targeting Trials Do Infant Subgroups Matter? Clin Perinatol 2019 doi.org/10.1016/j.clp.2019.05.003
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...
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 materially alter the relative effectiveness and ranking of treatments. The ‘comparison-adjusted’ funnel plot has been suggested to assess the presence of small-study effects. Model that adjusted for small-study effects should be performed if small-study effects was found.
References
1. Zeng L, Tian J, Song F, et al. Corticosteroids for the prevention of bronchopulmonary dysplasia in preterm infants: a networkmeta-analysis. Arch Dis Child Fetal Neonatal Ed. 2018 Nov;103(6):F506-F511.
2. Dias S, Caldwell DM. Network meta-analysis explained. Arch Dis Child Fetal Neonatal Ed. 2019 Jan;104(1):F8-F12.
3. Chaimani A, Higgins JP, Mavridis D, Spyridonos P, Salanti G. Graphical tools for network meta-analysis in STATA. PLoS One. 2013 Oct 3;8(10):e76654.
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...
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 airway management without need for intubation. Both explain how, and when, ETCO2 might be used highlighting limitations to its use. The European guidelines, on which UK guidelines are based, state “detection of exhaled carbon dioxide in addition to clinical assessment is recommended as the most reliable method to confirm tracheal placement in neonates with spontaneous circulation”. [5] Given this, considered and careful use of ETCO2 detection best sits within the Advanced Resuscitation of the Newborn Infant (ARNI) course which teaches care, including intubation, beyond Newborn Life Support.
References:
1. Charles E, Hunt K, Murthy V, Harris C, Greenough A. UK neonatal resuscitation survey. Arch Dis Child Fetal Neonatal Ed 2019;104:F324–F325
2. Oei JL, Saugstad OD, Lui K, Wright IM, Smyth JP, Craven P, Wang YA, McMullan R, Coates E, Ward M, Mishra P, De Waal K, Travadi J, See KC, Cheah IG, Lim CT, Choo YM, Kamar AA, Cheah FC, Masoud A, Tarnow-Mordi W. Targeted Oxygen in the Resuscitation of Preterm Infants, a Randomized Clinical Trial. Pediatrics 2017;139:e20161452.
3. Wyllie J, Perlman JM, Kattwinkel J, Wyckoff MH, Aziz K, Guinsburg R, Kim HS, Liley HG, Mildenhall L, Simon WM, Szyld E, Tamura M, Velaphi S; Neonatal Resuscitation Chapter Collaborators. Part 7: Neonatal resuscitation: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Resuscitation 2015;95:e169–201.
4. Welsford M, Nishiyama C, Shortt C, Weiner G, Roehr CC, Isayama T, Dawson JA, Wyckoff MH, Rabi Y; International Liaison Committee on Resuscitation Neonatal Life Support Task Force. Initial Oxygen Use for Preterm Newborn Resuscitation: A Systematic Review With Meta-analysis. Pediatrics 2019;143:e20181828.
5. Wyllie J, Bruinenberg J, Roehr CC, Rüdiger M, Trevisanuto D, Urlesberger B. European Resuscitation Council Guidelines for Resuscitation 2015: Section 7. Resuscitation and support of transition of babies at birth. Resuscitation 2015;95:249–63.
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...
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 surfactant and invasive ventilation, the reason for which is unclear.
Authors used FiO2 alone as a criterion for defining CPAP failure and positive end-expiratory pressure (PEEP) level was not considered. In such cases, many babies who can be managed by increasing PEEP may have got intubated even without adequate recruitment leading to increased intubation rates. This may explain the increased CPAP failure rates in the study population as compared to the historical cohort. On careful analysis of CPAP failure cases, the mean PEEP pressure was 6 cm only, which supports the above hypothesis.
Although, the trial intended to see the effect on intubation and mechanical ventilation, both of which have a direct effect on bronchopulmonary dysplasia (BPD) rates, the better primary outcome would have been the incidence of BPD.
Surprisingly the cesarean delivery rates very high in the study population.
Competing interests: None
Source of funding: None
References:
1. Minocchieri S, Berry CA, Pillow JJ. Nebulised surfactant to reduce severity of respiratory distress: a blinded, parallel, randomised controlled trial. Archives of Disease in Childhood - Fetal and Neonatal Edition. Published Online First: 26 July 2018. doi:10.1136/archdischild-2018-315051
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.
Huang et al recently summarised the role of human milk (HM) in bronchopulmonary dysplasia via a systematic review and meta-analysis of the available evidence. 1 With renewed interest in exclusive HM diets and various HM products now available, it is important for health professionals to have access to quality reviews of the evidence. We would like to make some observations on the Huang article, informed by our recent review. 2
There were two main differences in inclusion criteria between Huang’s review and ours: Huang et al included infants born <37 weeks’ gestation whereas ours was limited to very low birth weight infants. Huang et al also searched Chinese data-bases for studies in English and Chinese, in addition to conventional databases, partially addressing a limitation of our review which was restricted to studies published in English.
In their main results, Huang et al have combined RCTs and cohort studies with forest plots showing an overall protective effect of HM. However, in Table 3, in which data are presented by study design, no effect of HM from RCTs is evident. Thus, the overall protective effect is driven by the cohort studies alone. Cochrane methods recommend that different study designs should not be combined in a meta-analysis3 as they can be expected to differ systematically. By not reporting analyses of the different study designs, Huang et al overstate the benefits of HM.
In our recent meta-analysis 2 of human milk and morbidity...
Huang et al recently summarised the role of human milk (HM) in bronchopulmonary dysplasia via a systematic review and meta-analysis of the available evidence. 1 With renewed interest in exclusive HM diets and various HM products now available, it is important for health professionals to have access to quality reviews of the evidence. We would like to make some observations on the Huang article, informed by our recent review. 2
There were two main differences in inclusion criteria between Huang’s review and ours: Huang et al included infants born <37 weeks’ gestation whereas ours was limited to very low birth weight infants. Huang et al also searched Chinese data-bases for studies in English and Chinese, in addition to conventional databases, partially addressing a limitation of our review which was restricted to studies published in English.
In their main results, Huang et al have combined RCTs and cohort studies with forest plots showing an overall protective effect of HM. However, in Table 3, in which data are presented by study design, no effect of HM from RCTs is evident. Thus, the overall protective effect is driven by the cohort studies alone. Cochrane methods recommend that different study designs should not be combined in a meta-analysis3 as they can be expected to differ systematically. By not reporting analyses of the different study designs, Huang et al overstate the benefits of HM.
In our recent meta-analysis 2 of human milk and morbidity in very low birth weight infants, we used four comparisons: exclusive HM vs exclusive preterm formula (EPTF); any HM vs EPTF, high vs low dose of HM and pasteurised vs unpasteurised HM finding inconclusive evidence for an effect in all comparisons. The only significant finding was in the high vs low dose HM comparison for 18 cohort studies (RR 0.84 95% CI 0.73, 0.96), but with very low certainty. Findings from RCTs for this comparison were not significant and, taking evidence from both types of studies, we concluded a lack of evidence and that further studies may change the effect size seen.
Lastly, we are worried by the replication of data in each of the forest plots. The same five studies have been included (with the same number of events) in all six forest plots. It may be more appropriate to determine, where possible, the subgroup of the population studied that met each comparison criteria (i.e.: exclusive HM; exclusive formula; mainly HM; mainly formula; any HM) and enter the appropriate number of events and totals without repetition – or alternatively to enter each study into the one comparison that best suits their study protocol. It would be interesting to see how these changes to methods impact on the results.
References:
1. Huang J, Zhang L, Tang J, et al. Arch Dis Child Fetal Neonatal Ed Epub ahead of print: Human milk as a protective factor for bronchopulmonary dysplasia: a systematic review and meta-analysis [June 2018]. doi:10.1136/ archdischild-2017-314205
2. Miller J, Tonkin E, Damarell R et al. A Systematic Review and Meta-Analysis of Human Milk Feeding and Morbidity in Very Low Birth Weight Infants. Nutrients 2018, 10, 707; doi:10.3390/nu10060707
3. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.handbook.cochrane.org.
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...
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 outcome when the evidence from randomized and observational cohort studies were inconsistent. Miller et al stated that “the overall protective effect is driven by the cohort studies alone” in our review. However, this is not the case. In table 3, subgroup of RCT alone in all comparison showed a non-statistically significant trend towards protective effect of human milk on BPD. This meant the overall protective effect was not only driven by the cohort studies, but also attributed to the RCTs. RCTs undisputedly are on a higher level than observational studies. On the other hand, some of our most effective therapies are only supported by ‘lower-level’ observational studies, especially when the evidence from RCT is rare4. As conclusions in our review, we explicitly acknowledge the weakness of the evidence and that more RCTs are needed. A recent review for donor human milk on BPD also highlighted the benefit effect of human milk from observational studies, even though the effect from RCTs was not significant3.
Since neonates often received feeding with partial human milk due to a variety of reasons, paediatrician and parents pay close attention to the possible benefits of partial human milk feeding. One important aim of our review is to provide an overview of different portion/extent of human milk on BPD. In this setting, there are unavoidable overlaps in six categories: exclusive human milk (100% human milk), mainly human milk (50%≤human milk feeding<100%) and any human milk (0<human milk feeding≤100%); exclusive formula (100% formula feeding), mainly formula (50%≤formula feeding<100%) and any formula (0<formula feeding≤100%). A systematic review for human milk on retinopathy of prematurity also adopted the same method using replication of data 5.
We tried to avoid overlap by redefining two categories in our study to: any human milk (0<human milk feeding<50%) and any performed formula (0<human milk feeding<50%). Interestingly, our new meta-analysis only showed benefit from the comparision of exclusive human milk versus exclusive formula group [OR 0.78 (95% confidence interval 0.68 to 0.88)]. There was no statistical effect for other comparisons. Most comparisons included only one or two small studies. Overall, although we could not draw a definitive conclusion for maternal milk on BPD, limited evidence suggests further studies are necessary.
Competing interests None declared.
Reference
1. Cameron C, Fireman B, Hutton B, et al. Network meta-analysis incorporating randomized controlled trials and non-randomized comparative cohort studies for assessing the safety and effectiveness of medical treatments: challenges and opportunities. Systematic reviews 2015; 4: 147.
2. Verde PE, Ohmann C. Combining randomized and non-randomized evidence in clinical research: a review of methods and applications. Research synthesis methods 2015; 6: 45-62.
3. Villamor-Martinez E, Pierro M, Cavallaro G, et al. Donor human milk protects against bronchopulmonary dysplasia: a systematic review and meta-analysis. Nutrients 2018; 10: 238.
4. Verd S, Ginovart G. Human milk is perhaps the single most under-rated strategy to prevent bronchopulmonary dysplasia. Archives of disease in childhood Fetal and neonatal edition 2018 103: F599-f600.
5. Zhou J, Shukla VV, John D, et al. Human milk feeding as a protective factor for retinopathy of prematurity: a meta-analysis. pediatrics 2015; 136: e1576-86.
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?
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.
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.
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?
References:
Show More[1] Mitra S, Singh B, El-Naggar W, McMillan DD. Automated versus manual control of inspired oxygen to target oxygen saturation in prete...
Dear Editor,
Show MoreWe 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...
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 MoreWe 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.
Show MoreThe 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...
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.
Huang et al recently summarised the role of human milk (HM) in bronchopulmonary dysplasia via a systematic review and meta-analysis of the available evidence. 1 With renewed interest in exclusive HM diets and various HM products now available, it is important for health professionals to have access to quality reviews of the evidence. We would like to make some observations on the Huang article, informed by our recent review. 2
Show MoreThere were two main differences in inclusion criteria between Huang’s review and ours: Huang et al included infants born <37 weeks’ gestation whereas ours was limited to very low birth weight infants. Huang et al also searched Chinese data-bases for studies in English and Chinese, in addition to conventional databases, partially addressing a limitation of our review which was restricted to studies published in English.
In their main results, Huang et al have combined RCTs and cohort studies with forest plots showing an overall protective effect of HM. However, in Table 3, in which data are presented by study design, no effect of HM from RCTs is evident. Thus, the overall protective effect is driven by the cohort studies alone. Cochrane methods recommend that different study designs should not be combined in a meta-analysis3 as they can be expected to differ systematically. By not reporting analyses of the different study designs, Huang et al overstate the benefits of HM.
In our recent meta-analysis 2 of human milk and morbidity...
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...
Show MoreI 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?
Pages