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.

Implementation of Nationwide Evidence- and Consensus-Based Guidelines to Harmonize Neonatal Care in The Netherlands.

BACKGROUND: A Dutch committee for National Guidelines in Neonatology developed nineteen evidence- and consensus-based guidelines to be used in all Dutch neonatal intensive care units (NICUs). The primary goal was to make clinical practices more uniform and consistent. OBJECTIVE: This study investigated to what extent the guidelines were implemented and which factors played a role in implementation. STUDY DESIGN: A mixed method study design was used to investigate both the level and the process of implementation. A nationwide, multicenter, cross-sectional survey was performed using a validated instrument for measuring the level of implementation (Normalization MeAsure Development questionnaire, NoMAD). The number of implemented guidelines per NICU and the frequency and content of the amendments that NICUs made to the original consensus guidelines were analyzed. Through semi-structured interviews, perceived barriers and facilitators for implementation were explored. PARTICIPANTS: Fellows and neonatologists working at all ten Dutch level 3-4 NICUs were eligible. RESULTS: On an average, NICUs implemented 12.6 (of 19) guidelines (range 6-17). The Normalization Process Scale was 54 (of 65). Main influencing factors impeding implementation were guideline-related (e.g., unpractical, lengthy guidelines) and personal (e.g., an active representative responsible for local implementation). CONCLUSION: The implementation of our guidelines appears to be successful. Ways for improvement can be distinguished in personal, guideline-related and external factors. Empowerment of local representatives was considered most essential.

Neonatal Safety of Elective Family-Centered Caesarean Sections: A Cohort Study.

BACKGROUND: Although little data are available concerning safety for newborns, family-centered caesarean sections (FCS) are increasingly implemented. With FCS mothers can see the delivery of their baby, followed by direct skin-to-skin contact. We evaluated the safety for newborns born with FCS in the Leiden University Medical Center (LUMC), where FCS was implemented in June 2014 for singleton pregnancies with a gestational age (GA) ≥38 weeks and without increased risks for respiratory morbidity. METHODS: The incidence of respiratory pathology, unplanned admission, and hypothermia in infants born after FCS in LUMC were retrospectively reviewed and compared with a historical cohort of standard elective cesarean sections (CS). RESULTS: From June 2014 to November 2015, 92 FCS were performed and compared to 71 standard CS in 2013. Incidence of respiratory morbidity, hypothermia, temperatures at arrival at the department, GA, and birth weight were comparable (ns). Unplanned admission occurred more often after FCS when compared to standard CS (21 vs 7%; p = 0.03), probably due to peripheral oxygen saturation (SpO2) monitoring. There was no increase in respiratory pathology (8 vs 6%, ns). One-third of the babies were separated from their mother during or after FCS. CONCLUSION: Unplanned neonatal admissions after elective CS increased after implementing FCS, without an increase in respiratory morbidity or hypothermia. SpO2 monitoring might have a contribution. Separation from the mother occurred often.

Respiratory morbidity was an important consequence of prematurity in the first two years after discharge in three cohorts from 1996 to 2009.

AIM: This study aimed to evaluate the respiratory morbidity of preterm infants in the first two years after discharge in three cohorts from 1996 to 2009. METHODS: We included infants with a gestational age from 25 + 0 to 29 + 6 weeks, who were born in 1996-1997, 2003-2004 and 2008-2009 at the Leiden University Medical Center in the Netherlands. The following parameters were recorded: bronchopulmonary dysplasia (BPD), defined as oxygen demand or positive pressure at 36 weeks, mortality, duration of supplemental oxygen, discharge with supplemental oxygen and a nasogastric feeding tube, rehospitalisation and the use of inhaled medication. RESULTS: In line with our protocols, 106, 120 and 156 infants were analysed in the three study periods and 29%, 22% and 18% were diagnosed with BPD. Respiratory morbidity did not change over time in infants with and without BPD, except for an increase in rehospitalisation for respiratory issues in infants with BPD. This decreased in infants without BPD. Respiratory morbidity occurred more frequently in infants with BPD than without BPD, but this was not statistically significant. CONCLUSION: This study showed that when cohorts of preterm infants were compared over time, respiratory morbidity in the first two years of life remained an important consequence after discharge.

Monitoring Oxygenation and Gas Exchange in Neonatal Intensive Care Units: Current Practice in the Netherlands.

BACKGROUND: Although recommendations in oxygenation and gas exchange monitoring in the neonatal intensive care unit (NICU) are available, little is known of the current practice. AIM: To evaluate the current practice in oxygenation and gas exchange monitoring of the NICUs in the Netherlands. METHODS: An online survey-based questionnaire concerning preferences and current practice of monitoring oxygenation and gas exchange was sent out to all 107 neonatal staff members (neonatologists, neonatal fellows, and physician assistants) of the 10 NICUs in the Netherlands. RESULTS: The response rate was 42%. Pulse oximetry (PO), partial pressure of oxygen in arterial blood gas (paO2), and oxygen saturation in arterial blood gas (saO2) was used by, respectively, 100, 80, and 27% of the staff members for monitoring oxygenation. Of all staff members, 76% considered PO as the best parameter for monitoring oxygenation, 22% paO2, and 2% saO2. Blood gas, transcutaneous gas monitoring, endotracheal gas monitoring, and near-infrared spectroscopy was used by, respectively, 100, 82, 40, and 18% of the staff members for monitoring gas exchange. During endotracheal ventilation, 67% of the caregivers would exclusively accept arterial blood gas for gas exchange monitoring. In contrast, during non-invasive ventilation, 68% of the caregivers did not prefer arterial or capillary blood gas (CBG). CBG is found reliable in infants with warm extremities by 76% of the caregivers. Venous blood gas would be accepted by 60% of the caregivers, independent of the mode of respiratory support, and only when venous blood sample was needed for other reasons. CONCLUSION: This survey identified a wide variation in preference in monitoring oxygenation and gas exchange monitoring among Dutch neonatal staff members.