Physiological-based cord clamping in very preterm infants: the Aeration, Breathing, Clamping 3 (ABC3) trial-statistical analysis plan for a multicenter randomized controlled trial.

BACKGROUND: Mortality, cerebral injury, and necrotizing enterocolitis (NEC) are common complications of very preterm birth. An important risk factor for these complications is hemodynamic instability. Pre-clinical studies suggest that the timing of umbilical cord clamping affects hemodynamic stability during transition. Standard care is time-based cord clamping (TBCC), with clamping irrespective of lung aeration. It is unknown whether delaying cord clamping until lung aeration and ventilation have been established (physiological-based cord clamping, PBCC) is more beneficial. This document describes the statistical analyses for the ABC3 trial, which aims to assess the efficacy and safety of PBCC, compared to TBCC. METHODS: The ABC3 trial is a multicenter, randomized trial investigating PBCC (intervention) versus TBCC (control) in very preterm infants. The trial is ethically approved. Preterm infants born before 30 weeks of gestation are randomized after parental informed consent. The primary outcome is intact survival, defined as the composite of survival without major cerebral injury and/or NEC. Secondary short-term outcomes are co-morbidities and adverse events assessed during NICU admission, parental reported outcomes, and long-term neurodevelopmental outcomes assessed at a corrected age of 2 years. To test the hypothesis that PBCC increases intact survival, a logistic regression model will be estimated using generalized estimating equations (accounting for correlation between siblings and observations in the same center) with treatment and gestational age as predictors. This plan is written and submitted without knowledge of the data. DISCUSSION: The findings of this trial will provide evidence for future clinical guidelines on optimal cord clamping management at birth. TRIAL REGISTRATION: ClinicalTrials.gov NCT03808051. Registered on 17 January 2019.

Physiological-based cord clamping in very preterm infants: the Aeration, Breathing, Clamping 3 (ABC3) trial-study protocol for a multicentre randomised controlled trial.

BACKGROUND: International guidelines recommend delayed umbilical cord clamping (DCC) up to 1 min in preterm infants, unless the condition of the infant requires immediate resuscitation. However, clamping the cord prior to lung aeration may severely limit circulatory adaptation resulting in a reduction in cardiac output and hypoxia. Delaying cord clamping until lung aeration and ventilation have been established (physiological-based cord clamping, PBCC) allows for an adequately established pulmonary circulation and results in a more stable circulatory transition. The decline in cardiac output following time-based delayed cord clamping (TBCC) may thus be avoided. We hypothesise that PBCC, compared to TBCC, results in a more stable transition in very preterm infants, leading to improved clinical outcomes. The primary objective is to compare the effect of PBCC on intact survival with TBCC. METHODS: The Aeriation, Breathing, Clamping 3 (ABC3) trial is a multicentre randomised controlled clinical trial. In the interventional PBCC group, the umbilical cord is clamped after the infant is stabilised, defined as reaching heart rate > 100 bpm and SpO2 > 85% while using supplemental oxygen < 40%. In the control TBCC group, cord clamping is time based at 30-60 s. The primary outcome is survival without major cerebral and/or intestinal injury. Preterm infants born before 30 weeks of gestation are included after prenatal parental informed consent. The required sample size is 660 infants. DISCUSSION: The findings of this trial will provide evidence for future clinical guidelines on optimal cord clamping management in very preterm infants at birth. TRIAL REGISTRATION: ClinicalTrials.gov NCT03808051. First registered on January 17, 2019.

Endotracheal intubation skills of pediatricians versus anesthetists in neonates and children.

This study compares the performance of pediatricians and anesthetists in neonatal and pediatric endotracheal intubations (ETI) during simulated settings. Participants completed a questionnaire and performed an ETI scenario on a neonatal and a child manikin. The procedures were recorded with head cameras and cameras attached to standard laryngoscope blades. The outcomes were successful intubation, time to successful intubation, number of attempts, complications, total performance score, end-assessment rating, and an assessment whether the participant was sufficiently able to perform an ETI. Fifty-two pediatricians and 52 anesthetists were included. For the neonatal ETI, the rate of successful intubation was in favor of anesthetists although not significant. Anesthetists performed significantly better in all other outcomes. Of the pediatricians, 65% was rated sufficiently adept to perform a neonatal ETI vs 100% of the anesthetists. Pediatricians (29%) overestimated while anesthetists (33%) underestimated their performance in neonatal ETI. For the pediatric ETI, all outcomes were significantly better for anesthetists. Only 15% of all pediatricians were considered sufficiently able to perform pediatric ETI vs 94% of the anesthetists.Conclusion: Anesthetists are far more adept in performing ETI in neonates and children compared with pediatricians in a simulated setting. Complications are expected to occur less frequently and less seriously when anesthetists perform ETI. What is Known: • Endotracheal intubation (ETI) performed by inexperienced care providers can lead to unsuccessful and/or prolonged intubation attempts. This can cause complications such as hypoxemia, trauma to the oropharynx and larynx, and prolonged interruption of resuscitation, which results in a high morbidity/mortality. • Fifty to 60 real-life ETI procedures are needed before ETI can be performed with a 90% success rate. Despite this, 18% of providers still require some assistance even after performing 80 intubations. Skill fade will occur if there is too little exposure. What is New: • This study shows that, on both neonatal and child manikins, anesthetists perform better in ETI compared with pediatricians. Besides this, complications are expected to occur less frequently and less seriously when anesthetists are performing the ETIs on neonates and children. • In those countries where there are no clear interprofessional agreements made in general hospitals on who will perform ETI on neonates and children in acute care settings, these agreements are urgently necessary.

Dutch paediatrician's opinions about acute care for critically ill children in general hospitals.

UNLABELLED: Paediatricians in general hospitals have limited experience with critically ill children, due to the low incidence and their diversity in age, pathology and presentation. Consequently, adequate organization, training and materials and medication are of major importance. This voluntary and anonymous survey-based study was conducted to gain insight in the current status of these aspects. In June 2012, all 687 paediatricians employed at 84 general hospitals in The Netherlands received a hardcopy questionnaire with questions relating to demographics, organization, training and materials and medication concerning the acute care for critically ill children. Of the sent questionnaires, 41.3% were eligible for analysis. According to the organization of the acute care of critically ill children, 73.9% of the respondents indicated verbal agreements were made, of which 77.0% stated that these were recorded in written protocols. Taskforces were present according to 64.5% of our respondents. Of the respondents, 64.4% were Advanced Paediatric Life Support (APLS) certified. Of the stated training scenarios, 90.8% were available in their hospital, which were followed on a regular basis by 63.9% of the paediatricians. Paediatric resuscitation carts were present on both emergency department and paediatric ward according to 95.1%. Materials (37.7%) and medication (45.3%) were frequently lacking. CONCLUSION: Paediatricians from general hospitals in The Netherlands consider that acute care for critically ill children has to be improved in terms of organization, training and teamwork, and medication and materials. National guidelines concerning the organization and training may contribute to this improvement, as well as a standardized inventory list for paediatric resuscitation carts.