Trial of Selective Early Treatment of Patent Ductus Arteriosus with Ibuprofen.

BACKGROUND: The cyclooxygenase inhibitor ibuprofen may be used to treat patent ductus arteriosus (PDA) in preterm infants. Whether selective early treatment of large PDAs with ibuprofen would improve short-term outcomes is not known. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial evaluating early treatment (≤72 hours after birth) with ibuprofen for a large PDA (diameter of ≥1.5 mm with pulsatile flow) in extremely preterm infants (born between 23 weeks 0 days' and 28 weeks 6 days' gestation). The primary outcome was a composite of death or moderate or severe bronchopulmonary dysplasia evaluated at 36 weeks of postmenstrual age. RESULTS: A total of 326 infants were assigned to receive ibuprofen and 327 to receive placebo; 324 and 322, respectively, had data available for outcome analyses. A primary-outcome event occurred in 220 of 318 infants (69.2%) in the ibuprofen group and 202 of 318 infants (63.5%) in the placebo group (adjusted risk ratio, 1.09; 95% confidence interval [CI], 0.98 to 1.20; P = 0.10). A total of 44 of 323 infants (13.6%) in the ibuprofen group and 33 of 321 infants (10.3%) in the placebo group died (adjusted risk ratio, 1.32; 95% CI, 0.92 to 1.90). Among the infants who survived to 36 weeks of postmenstrual age, moderate or severe bronchopulmonary dysplasia occurred in 176 of 274 (64.2%) in the ibuprofen group and 169 of 285 (59.3%) in the placebo group (adjusted risk ratio, 1.09; 95% CI, 0.96 to 1.23). Two unforeseeable serious adverse events occurred that were possibly related to ibuprofen. CONCLUSIONS: The risk of death or moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age was not significantly lower among infants who received early treatment with ibuprofen than among those who received placebo. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Baby-OSCAR ISRCTN Registry number, ISRCTN84264977.).

Recommended Guideline for Uniform Reporting of Neonatal Resuscitation: The Neonatal Utstein Style.

Clinical research on neonatal resuscitation has accelerated over recent decades. However, an important methodologic limitation is that there are no standardized definitions or reporting guidelines for neonatal resuscitation clinical studies. To address this, the International Liaison Committee on Resuscitation Neonatal Life Support Task Force established a working group to develop the first Utstein-style reporting guideline for neonatal resuscitation. The working group modeled this approach on previous Utstein-style guidelines for other populations. This reporting guideline focuses on resuscitation of newborns immediately after birth for respiratory failure, bradycardia, severe bradycardia, or cardiac arrest. We identified 7 relevant domains: setting, patient, antepartum, birth/preresuscitation, resuscitation process, postresuscitation process, and outcomes. Within each domain, relevant data elements were identified as core versus supplemental. Core data elements should be collected and reported for all neonatal resuscitation studies, while supplemental data elements may be collected and reported using standard definitions when possible. The Neonatal Utstein template includes both core and supplemental elements across the 7 domains, and the associated Data Table provides detailed information and reporting standards for each data element. The Neonatal Utstein reporting guideline is anticipated to assist investigators engaged in neonatal resuscitation research by standardizing data definitions. The guideline will facilitate data pooling in meta-analyses, enhancing the strength of neonatal resuscitation treatment recommendations and subsequent guidelines.

Suctioning of clear amniotic fluid at birth: A systematic review.

Context: Upper airway suctioning at birth was considered standard procedure and is still commonly practiced. Negative effects could exceed benefits of suction. Question: In infants born through clear amniotic fluid (P) does suctioning of the mouth and nose (I) vs no suctioning (C) improve outcomes (O). Data sources: Information specialist conducted literature search (12th September 2021, re-run 17th June 2022) using Medline, Embase, Cochrane Databases, Database of Abstracts of Reviews of Effects, and CINAHL. RCTs, non-RCTs and observational studies with a defined selection strategy were included. Unpublished studies, reviews, editorials, animal and manikin studies were excluded. Data extraction: Two authors independently extracted data, risk of bias was assessed using the Cochrane ROB2 and ROBINS-I tools. Certainty of evidence was assed using the GRADE framework. Review Manager was used to analyse data and GRADEPro to develop summary of evidence tables. Meta-analyses were performed if ≥2 RCTs were available. Outcomes: Primary: assisted ventilation. Secondary: advanced resuscitation, oxygen supplementation, adverse effects of suctioning, unanticipated NICU admission. Results: Nine RCTs (n = 1096) and 2 observational studies (n = 418) were identified. Two RCTs (n = 280) with data concerns were excluded post-hoc. Meta-analysis of 3 RCTs, (n = 702) showed no difference in primary outcome. Two RCTs (n = 200) and 2 prospective observational studies (n = 418) found lower oxygen saturations in first 10 minutes of life with suctioning. Two RCTs (n = 200) showed suctioned newborns took longer to achieve target saturations. Limitations: Certainty of evidence was low or very low for all outcomes. Most studies selected healthy newborns limiting generalisability and insufficient data was available for planned subgroup analyses. Conclusions: Despite low certainty evidence, this review suggests no clinical benefit from suctioning clear amniotic fluid from infants following birth, with some evidence suggesting a resulting desaturation. These finding support current guideline recommendations that this practice is not used as a routine step in birth. Funding: The International Liaison Committee on Resuscitation provided access to software platforms, an information specialist and teleconferencing. Clinical Trial Registration: This systematic review was registered with the Prospective Register of Systematic Reviews (https://www.crd.york.ac.uk/prospero/) (identifier: CRD42021286258).

Tactile Stimulation in Newborn Infants With Inadequate Respiration at Birth: A Systematic Review.

CONTEXT: For many years the International Liaison Committee on Resuscitation has recommended the use of tactile stimulation for initial management of infants born with inadequate respiratory effort at birth without systematically examining its effectiveness. OBJECTIVE: Systematic review to compare the effectiveness of tactile stimulation with routine handling in newly born term and preterm infants. DATA SOURCES: Medline, Embase, Cochrane CENTRAL, along with clinical trial registries. STUDY SELECTION: Randomized and non-randomized studies were included based on predetermined criteria. DATA EXTRACTION: Data were extracted independently by authors. Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) was used to assess risk of bias in non-randomized studies. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to assess the certainty of evidence. RESULTS: Among 2455 unique articles identified, 2 observational studies were eligible and qualitatively summarized. Because one of the studies was at critical risk of bias, only the other study including 243 preterm infants on continuous positive airway pressure with clinical indications for tactile stimulation was analyzed. It showed a reduction in tracheal intubation in infants receiving tactile stimulation compared with no tactile stimulation (12 of 164 vs 14 of 79, risk ratio of 0.41 [95% confidence interval 0.20 to 0.85]); however, the certainty of evidence was very low. LIMITATIONS: The available data were limited and only from observational studies. CONCLUSIONS: A potential benefit of tactile stimulation was identified but was limited by the very low certainty of evidence. More research is suggested to evaluate the effectiveness as well as the optimal type and duration of tactile stimulation.

[Newborn resuscitation and support of transition of infants at birth]. / Versorgung und Reanimation des Neugeborenen nach der Geburt: Leitlinien des European Resuscitation Council 2021.

The European Resuscitation Council has produced these newborn life support guidelines, which are based on the International Liaison Committee on Resuscitation (ILCOR) 2020 Consensus on Science and Treatment Recommendations (CoSTR) for Neonatal Life Support. The guidelines cover the management of the term and preterm infant. The topics covered include an algorithm to aid a logical approach to resuscitation of the newborn, factors before delivery, training and education, thermal control, management of the umbilical cord after birth, initial assessment and categorisation of the newborn infant, airway and breathing and circulation support, communication with parents, considerations when withholding and discontinuing support.

Theoretical knowledge and skill retention 3 and 6 months after a European Newborn Life Support provider course.

INTRODUCTION: The European Resuscitation Council Newborn Life Support Course (ERC- NLS) aims at training healthcare professionals, involved in perinatal care, in order to intervene efficiently and promptly to assist transition or resuscitate neonates who require help at birth. However, limited data exists for the retention of the theoretical knowledge and practical skills provided by the course. This study aims to evaluate the degree of knowledge and skill retention 3 and 6 months after the ERC-NLS provider course. METHODS: This is a prospective study. Theoretical knowledge was evaluated using the ERC-approved NLS written test (50 True/False questions). Evaluation of technical skills included performance, on an Advanced Life Support neonatal maniquin (LAERDAL), of airway management, ventilation and support of circulation (21 detailed skills). The effect of certain factors on theoretical skill retention was also evaluated. RESULTS: One hundred and sixteen (n = 116) participants were initially recruited in the study (12 males and 104 females). Theoretical knowledge was evaluated in 113 participants (3 participants missed follow-up appointments) and technical skills in 80 participants. The mean score for theoretical knowledge was 86.24% ± 5.3, 80.88% ± 7.43 and 80.04% ± 7.04 at baseline, at 3 and 6 months, respectively. This difference was significant among the three time points (baseline vs 3 months: p < 0.001; baseline vs 6 months: p < 0.001; 3 month's vs 6 months: p = 0.034). Although gender did not have an effect, doctors and participants of higher education yielded higher score of success. Regarding technical skills, 9 skills showed a continuous decline of performance from baseline to 6 months, while no difference existed for 12 skills. CONCLUSIONS: Healthcare professionals after the NLS provider course retain satisfactory levels of theoretical knowledge and technical skills even at 6 months post-training, although, there is a decline compared to baseline. Further research is needed in order to establish the proper time and type of refreshment course in order to improve outcomes.

Archibald "Stewart" Hunter MBChB, FRCP(Ed) FRCP(Glas), DCH, 7 March, 1936-18 February, 2021.

Stewart Hunter was born in 1936 in Comrie, Perthshire. He was the son of Margaret (Peggy) and Archibald Hunter who was a minister in the Church of Scotland and later became Professor of New Testament Theology at the University of Aberdeen. Whilst Stewart chose medicine over the Kirk, he still studied at Aberdeen University. Following qualification in 1960, he chose to specialise in Paediatric Cardiology moving his family to London to learn how to treat children born with heart malformations at Great Ormond Street. Subsequently, he and the family moved back north to Edinburgh to continue that speciality at the Sick Children's Hospital. In 1969, he was appointed as a lecturer in paediatric cardiology in the academic department of Newcastle University. Between 1972 and 1973, he and the family went to a research post in the United States of America in Pennsylvania where he was part of a team researching and publishing on the use of cineangiography in adults, a technique which he then extended with Dr Mike Tynan to children and infants upon his return to Newcastle. He returned to a second consultant post at Newcastle General Hospital, where the North East Clinical Paediatric Cardiology department was sited before moving to the new purpose built department of Paediatric Cardiology at Freeman Hospital, Newcastle upon Tyne in 1977. His career is a list of achievements which is perhaps most notable for the many clinicians of varying backgrounds with whom he collaborated, supported, taught and developed over the years.

European Resuscitation Council Guidelines 2021: Newborn resuscitation and support of transition of infants at birth.

The European Resuscitation Council has produced these newborn life support guidelines, which are based on the International Liaison Committee on Resuscitation (ILCOR) 2020 Consensus on Science and Treatment Recommendations (CoSTR) for Neonatal Life Support. The guidelines cover the management of the term and preterm infant. The topics covered include an algorithm to aid a logical approach to resuscitation of the newborn, factors before delivery, training and education, thermal control, management of the umbilical cord after birth, initial assessment and categorisation of the newborn infant, airway and breathing and circulation support, communication with parents, considerations when withholding and discontinuing support.

Study protocol: baby-OSCAR trial: Outcome after Selective early treatment for Closure of patent ductus ARteriosus in preterm babies, a multicentre, masked, randomised placebo-controlled parallel group trial.

BACKGROUND: The question of whether to treat patent ductus arteriosus (PDA) early or wait until symptoms appear remains high on the research agenda for neonatal medicine. Around 7000 extremely preterm babies under 29 weeks' gestation are born in the UK every year. In 40% of cases the PDA will fail to close spontaneously, even by 4 months of age. Untreated PDA can be associated with several serious and life-threatening short and long-term complications. Reliable data to support clinical decisions about PDA treatment are needed to prevent serious complications in high risk babies, while minimising undue exposure of infants. With the availability of routine bedside echocardiography, babies with a large PDA can be diagnosed before they become symptomatic. METHODS: This is a multicentre, masked, randomised, placebo-controlled parallel group trial to determine if early-targeted treatment of a large PDA with parenteral ibuprofen in extremely preterm babies (23+ 0-28+ 6 weeks' gestation) improves short and long-term health and economic outcomes. With parental informed consent, extremely preterm babies (born between 23+ 0-28+ 6 weeks' gestation) admitted to tertiary neonatal units are screened using echocardiography. Babies with a large PDA on echocardiography, defined by diameter of at least 1.5 mm and unrestricted pulsatile PDA flow pattern, are randomly allocated to either ibuprofen or placebo within 72 h of birth. The primary endpoint is the composite outcome of death by 36 weeks' postmenstrual age or moderate or severe bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age. DISCUSSION: Prophylactic pharmacological treatment of all preterm babies unnecessarily exposes them to potentially serious side effects of drug treatment, when their PDA may have closed spontaneously. However, delaying treatment until babies become symptomatic could result in loss of treatment benefit as irreversible damage may have already been done. Targeted, early pharmacological treatment of PDA in asymptomatic babies has the potential to overcome the disadvantages of both prophylactic (overtreatment) and symptomatic approaches (potentially too late). This could result in improvements in the clinically important short-term clinical (mortality and moderate or severe BPD at 36 weeks' postmenstrual age) and long-term health outcomes (moderate or severe neurodevelopment disability and respiratory morbidity) measured at 2 years corrected age. TRIAL REGISTRATION: ISRCTN84264977 . Date assigned: 15/09/2010.

Family presence during resuscitation in paediatric and neonatal cardiac arrest: A systematic review.

CONTEXT: Parent/family presence at pediatric resuscitations has been slow to become consistent practice in hospital settings and has not been universally implemented. A systematic review of the literature on family presence during pediatric and neonatal resuscitation has not been previously conducted. OBJECTIVE: To conduct a systematic review of the published evidence related to family presence during pediatric and neonatal resuscitation. DATA SOURCES: Six major bibliographic databases was undertaken with defined search terms and including literature up to June 14, 2020. STUDY SELECTION: 3200 titles were retrieved in the initial search; 36 ultimately included for review. DATA EXTRACTION: Data was double extracted independently by two reviewers and confirmed with the review team. All eligible studies were either survey or interview-based and as such we turned to narrative systematic review methodology. RESULTS: The authors identified two key sets of findings: first, parents/family members want to be offered the option to be present for their child's resuscitation. Secondly, health care provider attitudes varied widely (ranging from 15% to >85%), however, support for family presence increased with previous experience and level of seniority. LIMITATIONS: English language only; lack of randomized control trials; quality of the publications. CONCLUSIONS: Parents wish to be offered the opportunity to be present but opinions and perspectives on the family presence vary greatly among health care providers. This topic urgently needs high quality, comparative research to measure the actual impact of family presence on patient, family and staff outcomes. PROSPERO REGISTRATION NUMBER: CRD42020140363.

Sustained Lung Inflations During Neonatal Resuscitation at Birth: A Meta-analysis.

CONTEXT: The International Liaison Committee on Resuscitation prioritized review of sustained inflation (SI) of the lung at birth. OBJECTIVE: To complete a systematic review and meta-analysis comparing strategies using 1 or more SI ≥1 second with intermittent inflations <1 second for newborns at birth. DATA SOURCES: Medline, Embase, and Evidence-Based Medicine Reviews were searched from January 1, 1946, to July 20, 2020. STUDY SELECTION: Studies were selected by pairs of independent reviewers in 2 stages. DATA EXTRACTION: Reviewers extracted data, appraised risk of bias, and assessed certainty of evidence for each outcome. RESULTS: Ten trials enrolling 1502 preterm newborns were included. Five studies included newborns who did not receive assisted ventilation at the outset. There were no differences between SI and control groups for death before discharge or key morbidities. For death within the first 2 days, comparing SI with the controls, risk ratio was 2.42 (95% confidence interval = 1.15-5.09). In subgroup analysis of preterm infants ≤28 + 0 weeks' gestation, for death before discharge, risk ratio was 1.38 (95% confidence interval = 1.00-1.91). Together, these findings suggest the potential for harm of SI. LIMITATIONS: The certainty of evidence was very low for death in the delivery room and low for all other outcomes. CONCLUSIONS: In this systematic review, we did not find benefit in using 1 or more SI >5 seconds for preterm infants at birth. SI(s) may increase death before discharge among the subgroup born ≤28 + 0 weeks' gestation. There is insufficient evidence to determine the likely effect of SI(s) on other key morbidities.

Neonatal Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

This 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations (CoSTR) for neonatal life support includes evidence from 7 systematic reviews, 3 scoping reviews, and 12 evidence updates. The Neonatal Life Support Task Force generally determined by consensus the type of evidence evaluation to perform; the topics for the evidence updates followed consultation with International Liaison Committee on Resuscitation member resuscitation councils. The 2020 CoSTRs for neonatal life support are published either as new statements or, if appropriate, reiterations of existing statements when the task force found they remained valid. Evidence review topics of particular interest include the use of suction in the presence of both clear and meconium-stained amniotic fluid, sustained inflations for initiation of positive-pressure ventilation, initial oxygen concentrations for initiation of resuscitation in both preterm and term infants, use of epinephrine (adrenaline) when ventilation and compressions fail to stabilize the newborn infant, appropriate routes of drug delivery during resuscitation, and consideration of when it is appropriate to redirect resuscitation efforts after significant efforts have failed. All sections of the Neonatal Resuscitation Algorithm are addressed, from preparation through to postresuscitation care. This document now forms the basis for ongoing evidence evaluation and reevaluation, which will be triggered as further evidence is published. Over 140 million babies are born annually worldwide (https://ourworldindata.org/grapher/births-and-deaths-projected-to-2100). If up to 5% receive positive-pressure ventilation, this evidence evaluation is relevant to more than 7 million newborn infants every year. However, in terms of early care of the newborn infant, some of the topics addressed are relevant to every single baby born.

Neonatal Life Support 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

This 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations (CoSTR) for neonatal life support includes evidence from 7 systematic reviews, 3 scoping reviews, and 12 evidence updates. The Neonatal Life Support Task Force generally determined by consensus the type of evidence evaluation to perform; the topics for the evidence updates followed consultation with International Liaison Committee on Resuscitation member resuscitation councils. The 2020 CoSTRs for neonatal life support are published either as new statements or, if appropriate, reiterations of existing statements when the task force found they remained valid. Evidence review topics of particular interest include the use of suction in the presence of both clear and meconium-stained amniotic fluid, sustained inflations for initiation of positive-pressure ventilation, initial oxygen concentrations for initiation of resuscitation in both preterm and term infants, use of epinephrine (adrenaline) when ventilation and compressions fail to stabilize the newborn infant, appropriate routes of drug delivery during resuscitation, and consideration of when it is appropriate to redirect resuscitation efforts after significant efforts have failed. All sections of the Neonatal Resuscitation Algorithm are addressed, from preparation through to postresuscitation care. This document now forms the basis for ongoing evidence evaluation and reevaluation, which will be triggered as further evidence is published. Over 140 million babies are born annually worldwide (https://ourworldindata.org/grapher/births-and-deaths-projected-to-2100). If up to 5% receive positive-pressure ventilation, this evidence evaluation is relevant to more than 7 million newborn infants every year. However, in terms of early care of the newborn infant, some of the topics addressed are relevant to every single baby born.

Duration of Resuscitation at Birth, Mortality, and Neurodevelopment: A Systematic Review.

CONTEXT: The International Liaison Committee on Resuscitation Neonatal Life Support Task Force reviewed evidence for the duration of cardiopulmonary resuscitation (CPR) for newborns immediately after birth. OBJECTIVE: To summarize evidence for ongoing CPR on the outcomes of survival, neurodevelopment, and the composite of survival without moderate or severe neurodevelopmental impairment (NDI). DATA SOURCES: Medline, Embase, Evidence-Based Medicine Reviews, Cumulative Index to Nursing and Allied Health Literature, and Scientific Electronic Library Online were searched between inception and February 29, 2020. STUDY SELECTION: Two independent reviewers selected studies of newborns with at least 10 minutes of asystole, bradycardia, or pulseless electrical activity for which CPR is indicated. DATA EXTRACTION: Two independent reviewers extracted data and appraised the risk of bias. RESULTS: In 16 eligible studies, researchers reported outcomes of 579 newborns born between 1982 and 2017. Within individual studies, 2% to 100% of infants survived to last follow-up (hospital discharge through 12 years). Summarized across studies, 237 of 579 (40.9%) newborns survived to last follow-up. In 13 studies, researchers reported neurodevelopmental outcomes of 277 newborns. Of these, 30 of 277 (10.8%) survived without moderate or severe impairment, and 240 of 277 (87%) met the composite outcome of death or NDI (191 died and 49 survived with moderate or severe impairment). LIMITATIONS: There was very low certainty of evidence because of risk of bias and inconsistency. CONCLUSIONS: Infants with ongoing CPR at 10 minutes after birth are at high risk for mortality and neurodisability, but survival without moderate or severe NDI is possible. One specified duration of CPR is unlikely to uniformly predict survival or survival without neuroimpairment.

How does the BAPM Framework for Practice on Perinatal Management of Extreme Preterm Birth Before 27 Weeks of Gestation impact delivery of Newborn Life Support? A Resuscitation Council UK response.

In October 2019, the British Association of Perinatal Medicine (BAPM) published a Framework1 and associated infographic2 for 'Practice on Perinatal Management of Extreme Preterm Birth Before 27 Weeks of Gestation' This outlined an approach, based on data from the UK and abroad, to assist clinicians in decision-making relating to perinatal care at ≤26+6 weeks gestation. Many frontline providers of delivery room care of extremely preterm infants will have completed a Resuscitation Council UK (RCUK) Newborn Life Support or Advanced Resuscitation of the Newborn Infant course. This RCUK response to the BAPM Framework highlights how this might impact on their approach.