Search

Introduction This study aimed to describe the prevalence and risk factors for respiratory complications in monochorionic twins with twin anaemia polycythaemia sequence (TAPS). Methods All neonates diagnosed with postnatal TAPS at our centre between 2002 and 2023 were included in this retrospective study. The primary outcome was the prevalence of respiratory complications, including respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD) and persistent pulmonary hypertension of the newborn (PPHN). Secondary outcomes included need of respiratory support during admission and a risk-factor analysis for adverse respiratory outcome. Results In our study of 100 postnatally diagnosed TAPS pregnancies, 32% (62/199) experienced RDS and 13% (25/199) had BPD, with no difference between donors and recipients. PPHN occurred in 7% of cases, more frequently in donors (11%, 11/100) than in recipients (3%, 3/100) (OR = 1.3, 95%CI 0.2-2.6). Lower gestational age at birth and severe fetal anaemia were found to be significant independent risk factors associated with PPHN in TAPS twins (OR = 0.3, 95%CI 0.1-0.5), respectively (OR = 1.9, 95%CI 0.8-3.1). Conclusion TAPS donor twins have a four-fold increased risk of PPHN due to anaemia compared to recipient twins. Given the life-threatening nature of PPHN, TAPS twins should be born in hospitals equipped to treat it., (The Author(s). Published by S. Karger AG, Basel.)

Background: Planned caesarean section (CS) is a risk factor for neonatal respiratory distress caused by a greater volume of airway liquid in the absence of uterine contractions.Performing a newly conceptualised knee-to-chest flexion (KCF) manoeuvre at birth, mimicking uterine contraction-induced flexion may aid in expelling excess lung liquid., Objectives: To test whether performing a KCF manoeuvre at birth is feasible in infants born after planned CS and to test whether KCF leads to visible expulsion of lung liquid., Methods: Single-centre prospective interventional study in term infants born by planned CS at Leiden University Medical Centre, Netherlands. KCF was performed for a maximum of 45 s. Baseline characteristics were collected, primary outcome was ability to perform KCF and secondary outcome was any visible expulsion of fluid., Results: In 39 infants (mean (SD) gestational age 38.0 (0.7) weeks, birth weight 3537 (440) g), KCF could be performed in 21/39 (54%), whereas 18/39 (46.2%) starting vigorous breathing before KCF could be performed. Notably, visible lung liquid expulsion occurred in 9/21 (43%) infants. KCF duration averaged 29 (18) s. In 13/21 (62 %), KCF was not performed as per standard operating procedure. No adverse events were reported., Conclusion: It is feasible to perform KCF at birth in a large proportion of term infants born by planned CS, with visible expulsion of liquid in a significant proportion of these infants. Training healthcare providers to perform a standardised KCF could increase feasibility and success. Further studies are needed to assess feasibility and effectiveness of KCF., Trial Registration Number: NL74285.058.20., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Intravenous epinephrine administration is preferred during neonatal resuscitation, but may not always be rapidly administered due to lack of equipment or trained staff. We aimed to compare the time to return of spontaneous circulation (ROSC) and post-ROSC haemodynamics between intravenous, endotracheal (ET) and intranasal (IN) epinephrine in severely asphyxic, bradycardic newborn lambs., Methods: After instrumentation, severe asphyxia (heart rate <60 bpm, blood pressure ~10 mm Hg) was induced by clamping the cord in near-term lambs. Resuscitation was initiated with ventilation followed by chest compressions. Lambs were randomly assigned to receive intravenous (0.02 mg/kg), ET (0.1 mg/kg) or IN (0.1 mg/kg) epinephrine. If ROSC was not achieved after three allocated treatment doses, rescue intravenous epinephrine was administered. After ROSC, lambs were ventilated for 60 min., Results: ROSC in response to allocated treatment occurred in 8/8 (100%) intravenous lambs, 4/7 (57%) ET lambs and 5/7 (71%) IN lambs. Mean (SD) time to ROSC was 173 (32) seconds in the intravenous group, 360 (211) seconds in the ET group and 401 (175) seconds in the IN group (p<0.05 intravenous vs IN). Blood pressure and cerebral oxygen delivery were highest in the intravenous group immediately post-ROSC (p<0.05), whereas the ET group sustained the highest blood pressure over the 60-min observation (p<0.05)., Conclusion: Our study supports neonatal resuscitation guidelines, highlighting intravenous administration as the most effective route for epinephrine. ET and IN epinephrine should only be considered when intravenous access is delayed or not feasible., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Aim: Cardiorespiratory events in preterm infants pose a major challenge in the Neonatal Intensive Care Unit as they require a prompt response. We aimed to describe caregivers' responses to these events., Methods: We performed a prospective observational study in 19 preterm infants (28 ± 2 weeks) on non-invasive respiratory support using video recordings of the inside of the incubator for 72 (55-72) h. Caregivers' responses to these events were then identified from the videos., Results: We recorded and assessed 1851 cardiorespiratory events with a median duration of 11.0 (5.0-23.0) s. No response was observed in the majority of the events (91.5%). In the remaining 8.5% events, caregivers responded by pausing the alarm, adjusting devices and/or providing tactile stimulation with an average response time of 25.4 (13.8-35.9) s. Stimulation was the most observed response and was applied in 38 different ways. On average, stimulation lasted 18.7 (11.6-44.6) s and the cardiorespiratory events were resolved 30.6 (19.5-47.6) s after stimulation started., Conclusion: Our study showed that cardiorespiratory events are common in preterm infants in the NICU, but often not followed by intervention of the caregiver. The indication, timing and execution of responses to cardiorespiratory events is highly variable., (© 2024 The Author(s). Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Objective: To examine the providers' perceptions and experiences on implementation of video review (VR) of procedures in the neonatal intensive care unit (NICU)., Design: Qualitative study using semi-structured interviews with neonatal care providers about their experiences with VR. Interviews were audio-recorded, transcribed and thematically analysed using the data analysis software Atlas.ti V.22.2., Setting: Providers working in the NICU of the Leiden University Medical Center were interviewed during implementation of VR., Results: In total, 28 NICU staff members were interviewed. The interviewed providers appreciated VR and valued the focus on a safe learning environment. Five overarching themes were identified: (1) added value: providers reported that VR is a powerful tool for reflection on daily practice and serves as a magnifying glass on practice, provides a helicopter view and VR with nursing and medical staff together led to new insights and was seen as highly valuable; (2) preconditions and considerations: the existing culture of trust on the NICU positively influenced providers' perception; (3) adjustment: it was recommended to first let providers attend a VR session, before being recorded; (4) experiences with VR: suggestions were made by the providers regarding the preparation and organisation of VR and the role of the chair; (5) embedding VR: providers considered how to embed VR on the long-term while maintaining a safe learning environment and provided suggestions for expanding., Conclusion: Neonatal care providers appreciated the use of VR and provided viewpoints on how to implement VR successfully, which were used to develop a roadmap with recommendations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To compare the effect of peripheral oxygen saturation (SpO 2 ) target range (TR) (either 91%-95% and 92%-96%) on the frequency and duration of hypoxic and hyperoxic episodes while on automated oxygen control using the OxyGenie controller., Design: Randomised cross-over study., Setting: Tertiary-level neonatal unit in the Netherlands., Patients: Infants (n=27) with a median (IQR) gestational age of 27+0 (25+5-27+3) weeks and postnatal age of 16 (10-22) days, receiving invasive or non-invasive respiratory support., Interventions: In both groups supplemental oxygen was titrated to a TR of 91%-95% (TR low ) or 92%-96% (TR high ) by the OxyGenie controller (SLE6000 ventilator) for 24 hours each, in random sequence. After a switch in TR, a 1-hour washout period was applied to prevent carry-over bias., Main Outcome Measures: Frequency and duration of hypoxic (SpO 2 <80% for ≥1 s) and hyperoxic episodes (SpO 2 >98% for ≥1 s)., Results: Hypoxic episodes were less frequent when the higher range was targeted (TR high vs TR low : 2.5 (0.7-6.2)/hour vs 2.4 (0.9-10.2)/hour, p=0.02), but hyperoxic episodes were more frequent (5.3 (1.8-12.3)/hour vs 2.9 (1.0-7.1)/hour, p<0.001). The duration of the out-of-range episodes was not significantly different (hypoxia: 4.7 (2.8-7.1) s vs 4.4 (3.7-6.5) s, p=0.67; hyperoxia: 4.3 (3.3-4.9) s vs 3.9 (2.8-5.5) s, p=0.89)., Conclusion: Targeting a higher SpO 2 TR with the OxyGenie controller reduced hypoxic episodes but increased hyperoxic episodes. This study highlights the feasibility of using an automated oxygen titration device to explore the effects of subtle TR adjustments on clinical outcomes in neonatal care., Trial Registration Number: NL9662., Competing Interests: Competing interests: ABtP has received an unrestricted research grant from Inspiration Healthcare., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Transitional circulation is normally transient after birth but can vary markedly between infants. It is actually in a state of transition between fetal (in utero) and neonatal (postnatal) circulation. In the absence of definitive clinical trials, information from applied physiological studies can be used to facilitate clinical decision making in the presence of hemodynamic compromise. This review summarizes the peculiar physiological features of the circulation as it transitions from one phenotype into another in term and preterm infants. The common causes of hemodynamic compromise during transition, intact umbilical cord resuscitation, and advanced hemodynamic monitoring are discussed. IMPACT: Transitional circulation can vary markedly between infants. There are alterations in preload, contractility, and afterload during the transition of circulation after birth in term and preterm infants. Hemodynamic monitoring tools and technology during neonatal transition and utilization of bedside echocardiography during the neonatal transition are increasingly recognized. Understanding the cardiovascular physiology of transition can help clinicians in making better decisions while managing infants with hemodynamic compromise. The objective assessment of cardio-respiratory transition and understanding of physiology in normal and disease states have the potential of improving short- and long-term health outcomes., (© 2023. The Author(s).)

Background: Early-onset Group B Streptococcus (EOGBS) infection leads to substantial morbidity and mortality in newborn infants. Intrapartum antibiotic prophylaxis (IAP) prevents EOGBS infection, but IAP strategies vary. The approach to the provision of IAP can be risk-based, universal or a combination of the two strategies. Previous systematic reviews reported that universal strategies might be most optimal in lowering EOGBS infection, but there is no consensus. Therefore, we aimed to provide up-to-date evidence on effectiveness of different strategies by comparing perinatal outcomes., Methods: A systematic search for EOGBS prevention strategies was performed in MEDLINE, Embase and Web of Science on May 2024. Studies were included if they reported on different strategies and outcomes of interest, including EOGBS infection, IAP administration and antimicrobial resistance regardless of publication date. Summary data was extracted from published reports. Study quality was assessed using the ROBINS-I tool. Random-effects meta-analyses were used to determine risk ratios (RR) and 95%-confidence intervals. PROSPERO registration CRD42023411806., Findings: A total of 6293 records were identified, of which 72 observational studies were included for synthesis with more than 10 million live births. Meta-analysis demonstrated that implementation of any strategy (n = 34 studies, RR 0.46 (0.36-0.60)), risk-based strategies (n = 11 studies, RR 0.65 (0.48-0.87)), or universal strategies (n = 16 studies, RR 0.37 (0.25-0.55)) was associated with a reduced risk of EOGBS infection compared to no strategy. In direct comparison, universal strategies were associated with a reduced risk of EOGBS compared to a risk-based strategy (n = 17 studies, RR 0.41 (0.30-0.55)), while the proportion of women receiving IAP did not differ between risk-based (16%) and universal (21%) strategies (n = 9 studies, RR 1.29 (0.95-1.75)). There was no antimicrobial resistance of EOGBS isolates to penicillin or ampicillin (n = 11 studies)., Interpretation: Any IAP strategy could reduce the risk of EOGBS infection without evidence of increasing antimicrobial resistance. Universal strategies give the largest reduction in the EOGBS burden, while not exposing a significantly higher proportion of pregnancies to IAP compared to risk-based strategies., Funding: UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction, a cosponsored programme executed by the World Health Organization., Competing Interests: Authors have no competing or conflicts of interests to declare., (© 2024 The Author(s).)

Background: As very preterm infants have surfactant-deficient and highly incompliant lungs, slowing lung deflation during expiration might help preserve functional residual capacity(FRC) during lung aeration. In this study, we investigated the effect of expiratory resistance(Re) on lung aeration during positive pressure ventilation in preterm rabbits immediately after birth., Methods: Preterm rabbit pups were delivered at 29 days gestation, mechanically ventilated from birth and simultaneously imaged to measure lung aeration using phase-contrast X-ray. Re was varied by altering the length (0, 60 or 1000 mm) of the expiratory circuit., Results: Increasing Re led to a decrease in lung deflation rates and both peak expiratory flows and flow rates at mid-deflation. As a result, the rate of de-acceleration(slowing) in lung deflation when approaching FRC was markedly reduced with increasing resistance. During lung aeration, FRC was significantly different between resistance groups and was significantly higher over time in the high compared to the low resistance group. While FRC values tended to be higher with higher Re, they were not significantly different at end-ventilation (t = 7 min)., Conclusion: Increasing Re of the ventilation circuit during lung aeration in preterm rabbits immediately after birth decreased lung deflation rates and increased the accumulation of FRC over time., Impact: The expiratory phase of the ventilatory cycle has been largely overlooked as an opportunity to improve ventilation in preterm infants after birth. Increasing the expiratory resistance of the ventilator circuit during lung aeration in preterm rabbits immediately after birth markedly decreased lung deflation rates and increased FRC accumulation, compared to a low expiratory resistance. This indicates that ventilation devices that reduce the "work of breathing" by reducing the expiratory resistance, may have the unintended effect of reducing FRC, particularly in extremely preterm infants that have surfactant deficient highly incompliant lungs., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: The goal of every medical team is to provide optimal care for their patients. We aimed to use video review (VR) sessions to identify and address areas for improvement in neonatal care., Methods: For nine months, neonatal procedures (stabilization at birth, intubations and sterile line insertions) were video recorded and reviewed with the neonatal care providers. Action research was used to identify and address areas for improvement which were categorized as (1) protocol/equipment adjustments, (2) input for research, (3) aspects of variety, or (4) development of educational material or training programs., Results: Eighteen VR sessions were organized with a mean(SD) of 17(5) staff members participating. In total, 120 areas for improvement were identified and addressed, of which 84/120 (70%) were categorized as aspects of variety, 20/120 (17%) as development of educational material or training programs, 10/120 (8%) as protocol/equipment adjustments, and 6/120 (5%) as input for research. The areas for improvement were grouped in themes per category, including sterility, technique, equipment, communication, teamwork, parents' perspective and ventilation., Conclusion: Our study showed that regularly organized VR empowered healthcare providers to identify and address a large variety of areas for improvement, contributing to continuous learning and improvement processes., Impact: Video review empowered healthcare providers to identify areas for improvement in neonatal care Video review gave providers the opportunity to address identified areas for improvement, either by enhancing the application of external evidence (i.e. guidelines), learning from individual clinical expertise or strengthening resilience and teamwork Embedding regularly organized video review sessions allowed for continuous monitoring of care by providers, which can be beneficial for creating ongoing learning and improvement processes The structured pathways, supporting implementation of changes that were proposed based on the video review sessions, could help other centers make use of the potential video review has to offer., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Manual tactile stimulation is used to counteract apnea in preterm infants, but it is unknown when this intervention should be applied. We compared an anticipatory to a reactive approach using vibrotactile stimulation to prevent hypoxia induced apneas., Methods: Preterm rabbit kittens were prematurely delivered and randomized to either group. All kittens breathed spontaneously with a positive airway pressure of 8 cmH 2 O while they were imaged using phase contrast X-ray. Irregular breathing (IB) was induced using gradual hypoxia. The anticipatory group received stimulation at the onset of IB and the reactive group if IB transitioned into apnea. Breathing rate (BR), heart rate (HR) and functional residual capacity (FRC) were compared., Results: Anticipatory stimulation significantly reduced apnea incidence and maximum inter-breath intervals and increased BR following IB, compared to reactive stimulation. Recovery in BR but not HR was more likely with anticipatory stimulation, although both BR and HR were significantly higher at 120 s after stimulation onset. FRC values and variability were not different., Conclusions: Anticipated vibrotactile stimulation is more effective in preventing apnea and enhancing breathing when compared to reactive stimulation in preterm rabbits. Stimulation timing is likely to be a key factor in reducing the incidence and duration of apnea., Impact: Anticipated vibrotactile stimulation can prevent apnea and stimulate breathing effort in preterm rabbits. Anticipated vibrotactile stimulation increases the likelihood of breathing rate recovery following hypoxia induced irregular breathing, when compared to reactive stimulation. Automated stimulation in combination with predictive algorithms may improve the treatment of apnea in preterm infants., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Video review (VR) of procedures in the medical environment can be used to drive quality improvement. However, first it has to be implemented in a safe and effective way. Our primary objective was to (re)define a guideline for implementing interprofessional VR in a neonatal intensive care unit (NICU). Our secondary objective was to determine the rate of acceptance by providers attending VR. For 9 months, VR sessions were evaluated with a study group, consisting of different stakeholders. A questionnaire was embedded at the end of each session to obtain feedback from providers on the session and on the safe learning environment. In consensus meetings, success factors and preconditions were identified and divided into different factors that influenced the rate of adoption of VR. The number of providers who recorded procedures and attended VR sessions was determined. A total of 18 VR sessions could be organised, with an equal distribution of medical and nursing staff. After the 9-month period, 101/125 (81%) of all providers working on the NICU attended at least 1 session and 80/125 (64%) of all providers recorded their performance of a procedure at least 1 time. In total, 179/297 (61%) providers completed the questionnaire. Almost all providers (99%) reported to have a positive opinion about the review sessions. Preconditions and success factors related to implementation were identified and addressed, including improving the pathway for obtaining consent, preparation of VR, defining the role of the chair during the session and building a safe learning environment. Different strategies were developed to ensure findings from sessions were used for quality improvement. VR was successfully implemented on our NICU and we redefined our guideline with various preconditions and success factors. The adjusted guideline can be helpful for implementation of VR in emergency care settings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

High concentrations of oxygen are often needed to optimize oxygenation in infants with persistent pulmonary hypertension (PPHN), but this can also increase the risk of hyperoxemia. We determined the occurrence of hyperoxemia in infants treated for PPHN. Medical records of infants ≥ 34 + 0 weeks gestational age (GA) who received inhaled nitric oxide (iNO) were retrospectively reviewed for oxygenation parameters during iNO therapy. Oxygen was manually titrated to target arterial oxygen tension (PaO 2 ) 10-13 kPa and peripheral oxygen saturation (SpO 2 ) 92-98%. The main study outcomes were the incidence and duration of hyperoxemia and hypoxemia and the fraction of inspired oxygen (FiO 2 ). A total of 181 infants were included. The median FiO 2 was 0.43 (IQR 0.34-0.56) and the maximum FiO 2 was 1.0 in 156/181 (86%) infants, resulting in at least one PaO 2  > 13 kPa in 149/181 (82%) infants, of which 46/149 (31%) infants had minimal one PaO 2  > 30 kPa. SpO 2 was > 98% in 179/181 (99%) infants for 17.7% (8.2-35.6%) of the iNO time. PaO 2  < 10 kPa occurred in 160/181 (88%) infants, of which 81/160 (51%) infants had minimal one PaO 2  < 6.7 kPa. SpO 2 was < 92% in 169/181 (93%) infants for 1.6% (0.5-4.3%) of the iNO time.    Conclusion: While treatment of PPHN is focused on preventing and reversing hypoxemia, hyperoxemia occurs inadvertently in most patients. What is Known: • High concentrations of oxygen are often needed to prevent hypoxemia-induced deterioration of PPHN, but this can also increase the risk of hyperoxemia. • Infants with persistent pulmonary hypertension may be particularly vulnerable to the toxic effects of oxygen, and hyperoxemia could further induce pulmonary vasoconstriction, potentially worsening the condition. What is New: • Hyperoxemia occurs in the majority of infants with PPHN during treatment with iNO. • Infants with PPHN spent a considerably longer period with saturations above the target range compared to saturations below the target range., (© 2024. The Author(s).)

Introduction: Recent evidence indicates that respiratory distress (RD) in near-term infants is caused by elevated airway liquid (EL) volume at the beginning of air-breathing after birth. While the adverse effects EL volumes on newborn lung function are known, the effects on respiratory control and breathing patterns shortly after birth (<4 h) are unknown. We investigated the effects of EL volumes on cardiorespiratory function and breathing patterns in spontaneously breathing near-term newborn lambs in the first hours after birth., Methods: At 137-8 days gestation (2-3 days prior to delivery; term ∼147 days), sterile surgery was performed on fetal sheep ( n  = 17) to implant catheters and blood flow probes. At 140 days, lambs were delivered via caesarean section under spinal anaesthesia. Airway liquid volumes were adjusted to mimic the level expected following vaginal delivery (∼10 ml/kg; Controls; n  = 7), or elective caesarean section (∼30 ml/kg; elevated airway liquid group; EL; n  = 10). Spontaneous breathing and cardiorespiratory parameters were recorded over four hours after birth. Non-invasive respiratory support with supplemental oxygen was provided if required., Results: EL lambs required higher inspired oxygen levels ( p  = 0.0002), were less active ( p  = 0.026), fed less ( p  = 0.008) and had higher respiratory morbidity scores than Controls ( p  < 0.0001). EL lambs also displayed higher rates of breathing patterns associated with RD, such as expiratory braking and tachypnoea. These patterns were particularly evident in male EL lambs who displayed higher levels of severe respiratory morbidity (e.g., expiratory braking) than female EL lambs., Conclusion: The study demonstrates that EL volumes at birth trigger respiratory behaviour and breathing patterns that resemble clinically recognised features of RD in term infants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Davies, Crossley, McGillick, Nitsos, Rodgers, Thiel, Zahra, Badurdeen, te Pas and Hooper.)

Background: Infants born with congenital diaphragmatic hernia (CDH) are at high risk of respiratory insufficiency and pulmonary hypertension. Routine practice includes immediate clamping of the umbilical cord and endotracheal intubation. Experimental animal studies suggest that clamping the umbilical cord guided by physiological changes and after the lungs have been aerated, named physiological-based cord clamping (PBCC), could enhance the fetal-to-neonatal transition in CDH. We describe the statistical analysis plan for the clinical trial evaluating the effects of PBCC versus immediate cord clamping on pulmonary hypertension in infants with CDH (PinC trial)., Design: The PinC trial is a multicentre, randomised controlled trial in infants with isolated left-sided CDH, born ≥ 35.0 weeks of gestation. The primary outcome is the incidence of pulmonary hypertension in the first 24 h after birth. Maternal outcomes include estimated maternal blood loss. Neonatal secondary outcomes include mortality before discharge, extracorporeal membrane oxygenation therapy, and number of days of mechanical ventilation. Infants are 1:1 randomised to either PBCC or immediate cord clamping using variable random permutated block sizes (4-8), stratified by treatment centre and estimated severity of pulmonary hypoplasia (i.e. mild/moderate/severe). At least 140 infants are needed to detect a relative reduction in pulmonary hypertension by one third, with 80% power and 0.05 significance level. A chi-square test will be used to evaluate the hypothesis that PBCC decreases the occurrence of pulmonary hypertension. This plan is written and submitted without knowledge of the collected data. The trial has been ethically approved., Trial Registration: ClinicalTrials.gov NCT04373902 (registered April 2020)., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

Airway liquid is cleared into lung tissue after birth, which becomes edematous and forces the chest wall to expand to accommodate both the cleared liquid and incoming air. This study investigated how changing chest wall mechanics affects respiratory function after birth in near-term lambs with different airway liquid volumes. Surgically instrumented near-term lambs (139 ± 2 days) were randomized into Control ( n = 7) or Elevated Liquid (EL; n = 6) groups. Control lambs had lung liquid drained to simulate expected volumes following vaginal delivery. EL lambs had airway liquid drained and 30 mL/kg liquid returned to simulate expected airway liquid volumes after elective cesarean section. Lambs were delivered, transferred to a Perspex box, and ventilated (30 min). Pressure in the box was adjusted to apply positive (7-8 cmH 2 O above atmospheric pressure) or negative (7-8 cmH 2 O below atmospheric pressure) pressures for 30 min before pressures were reversed. External negative pressures expanded the chest wall, reduced chest wall compliance ( C CW ) and increased lung compliance ( C L ) in Control and EL lambs. External positive pressures compressed the chest wall, increased C CW and reduced C L in Control and EL lambs. External negative pressure improved pulmonary oxygen exchange, reducing the alveolar-arterial difference in oxygen (AaDO 2 ) by 69 mmHg (95% CI [13, 125]; P = 0.016) in Control lambs and by 300 mmHg (95% CI [233, 367]; P < 0.001) in EL lambs. In contrast, external positive pressures impaired pulmonary gas exchange, increasing the AaDO 2 by 179 mmHg (95% CI [73, 285]; P = 0.002) in Control and by 215 mmHg (95% CI [89, 343]; P < 0.001) in EL lambs. The application of external thoracic pressures influences respiratory function after birth. NEW & NOTEWORTHY This study investigated how changes in chest wall mechanics influence respiratory function after birth. Our data indicate that the application of continuous external subatmospheric pressure greatly improves respiratory function in near-term lambs with respiratory distress, whereas external positive pressures impair respiratory function. Our findings indicate that, during neonatal resuscitation at birth, the forces applied to the chest wall should not be ignored as they can have a major impact on neonatal respiratory function.

To improve care for extremely premature infants, the development of an extrauterine environment for newborn development is being researched, known as Artificial Placenta and Artificial Womb (APAW) technology. APAW facilitates extended development in a liquid-filled incubator with oxygen and nutrient supply through an oxygenator connected to the umbilical vessels. This setup is intended to provide the optimal environment for further development, allowing further lung maturation by delaying gas exposure to oxygen. This innovative treatment necessitates interventions in obstetric procedures to transfer an infant from the native to an artificial womb, while preventing fetal-to-neonatal transition. In this narrative review we analyze relevant fetal physiology literature, provide an overview of insights from APAW studies, and identify considerations for the obstetric procedure from the native uterus to an APAW system. Lastly, this review provides suggestions to improve sterility, fetal and maternal well-being, and the prevention of neonatal transition., Competing Interests: The authors JvH, FD, SO have a patent application entitled “Transfer of a preterm baby from a natural womb” (no. WO2023027584A1). The authors JvH, FD, MvH, SO have a patent application entitled “Transfer of a preterm baby from a natural womb” (no. WO2022066014). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 van Haren, Delbressine, Schoberer, te Pas, van Laar, Oei and van der Hout-van der Jagt.)

Background: Infants with a congenital diaphragmatic hernia (DH) have underdeveloped lungs and require mechanical ventilation after birth, but the optimal approach is unknown. We hypothesised that sustained inflation (SI) increases lung aeration in newborn kittens with a DH., Methods: In pregnant New Zealand white rabbits, a left-sided DH was induced in two fetal kittens per doe at 24-days gestation (term = 32 days); litter mates acted as controls. DH and control kittens were delivered by caesarean section at 30 days, intubated and mechanically ventilated (7-10 min) with either an SI followed by intermittent positive pressure ventilation (IPPV) or IPPV throughout. The rate and uniformity of lung aeration was measured using phase-contrast X-ray imaging., Results: Lung weights in DH kittens were ~57% of controls. An SI increased the rate and uniformity of lung aeration in DH kittens, compared to IPPV, and increased dynamic lung compliance in both control and DH kittens. However, this effect of the SI was lost when ventilation changed to IPPV., Conclusion: While an SI improved the rate and uniformity of lung aeration in both DH and control kittens, greater consideration of the post-SI ventilation strategy is required to sustain this benefit., Impact: Compared to intermittent positive pressure ventilation (IPPV), an initial sustained inflation (SI) increased the rate and uniformity of lung aeration after birth. However, this initial benefit is rapidly lost following the switch to IPPV. The optimal approach for ventilating CDH infants at birth is unknown. While an SI improves lung aeration in immature lungs, its effect on the hypoplastic lung is unknown. This study has shown that an SI greatly improves lung aeration in the hypoplastic lung. This study will guide future studies examining whether an SI can improve lung aeration in infants with a CDH., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Balloon atrial septostomy (BAS) is an emergent and essential cardiac intervention to enhance intercirculatory mixing at atrial level in deoxygenated patients diagnosed with transposition of the great arteries (TGA) and restrictive foramen ovale. The recent recall of several BAS catheters and the changes in the European legal framework for medical devices (MDR 2017/745), has led to an overall scarcity of BAS catheters and raised questions about the use, safety, and experience of the remaining NuMED Z-5 BAS catheter., Aims: To evaluate and describe the practice and safety of the Z-5 BAS catheter, and to compare it to the performance of other BAS catheters., Methods: A retrospective single-center cohort encompassing all BAS procedures performed with the Z-5 BAS catheter in TGA patients between 1999 and 2022., Results: A total of 182 BAS procedures were performed in 179 TGA-newborns at Day 1 (IQR 0-5) days after birth, with median weight of 3.4 (IQR 1.2-5.7) kg. The need for BAS was urgent in 90% of patients. The percentage of BAS procedures performed at bedside increased over time from 9.8% (before 2010) to 67% (2017-2022). Major complication rate was 2.2%, consisting of cerebral infarction (1.6%) and hypovolemic shock (0.5%). The rate of minor complications was 9.3%, including temporary periprocedural AV-block (3.8%), femoral vein thrombosis (2.7%), transient intracardiac thrombus (0.5%), and atrial flutter (2.2%). BAS procedures performed at bedside and in the cardiac catheterization laboratory had similar complication rates., Conclusions: BAS using the Z-5 BAS catheter is both feasible and safe at bedside and at the cardiac catheterization laboratory with minimal major complications., (© 2023 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Background: The timing of cord clamping has become a focal point for neonatal caregivers due to the promising outcomes associated with delayed cord clamping, which is a simple and cost-effective method to enhance the survival and well-being of preterm infants. While initially the rationale behind delaying clamping was to facilitate increased placental transfusion, research has unveiled additional hemodynamic benefits., Summary: Experimental studies have demonstrated improved circulatory transition when clamping is postponed until the lungs are adequately aerated. This suggests that infants requiring assistance during the transition phase may benefit from stabilization while still attached to the cord. The Aeration, Breathing, and then Clamping (ABC) project aimed to translate these experimental findings into clinical practice., Key Message: In this review, we will discuss the insights gained and lessons learned from the project's implementation., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Aim: Studies in animals have shown that vocal cords (VCs) close during apnoea before and after birth, thereby impairing the effect of non-invasive ventilation. We tested the feasibility of visualising VCs using ultrasonography (US) and investigated the position and movement of the VCs during non-invasive respiratory support of preterm infants at birth., Methods: In an observational study, VCs were visualised using US in infants <30 weeks gestation during both stabilisation after birth and at one hour after birth. Respiratory efforts were simultaneously recorded. The percentage of time the VCs were closed in the first ten minutes was determined from videoframes acquired at 15 Hz and compared with respiratory flow patterns measured using a respiratory function monitor., Results: US of the VCs could be performed in 20/20 infants included (median (IQR) gestational age 27 +6 (27 +1 -28 +6 ) weeks) without interfering with stabilisation, of whom 60% (12/20) were initially breathing and 40% (8/20) were apnoeic at birth. In breathing infants, the VCs closed between breaths and during breath holds, which accounted for 57% (49-66) of the time. In apnoeic infants receiving positive pressure ventilation, the VCs were closed for 93% (81-99) of the time. US at one hour after birth could be performed in 14/20 infants, VCs were closed between breaths and during breath holds, accounting for 46% (27-52) of the time., Conclusion: Visualising VCs in preterm infants at birth using US is feasible. The VCs were closed during apnoea, in between breaths and during breath holds, impairing the effect of ventilation given., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: During stabilisation of preterm infants at birth, a face mask is used to provide respiratory support. However, application of these masks may activate cutaneous stretch receptors of the trigeminal nerve, causing apnoea and bradycardia. This study investigated the amount of force exerted on the face mask during non-invasive ventilation of preterm infants at birth and whether the amount of exerted force is associated with apnoea and bradycardia., Methods: A prospective observational study was performed in preterm infants born <32 weeks of gestation who were stabilised at birth. During the first 10 minutes of respiratory support, we measured breathing and heart rate as well as the amount of force exerted on a face mask using a custom-made pressure sensor placed on top of the face mask., Results: Thirty infants were included (median (IQR) gestational age(GA) 28 +3 (27 +0 -30 +0 ) weeks, birthweight 1104 (878-1275) grams). The median exerted force measured was 297 (198-377) grams, ranging from 0 to 1455 grams. Significantly more force was exerted on the face mask during positive pressure ventilation when compared to CPAP (410 (256-556) vs 286 (190-373) grams, p = 0.009). In a binary logistic regression model, higher forces were associated with an increased risk of apnoea (OR = 1.607 (1.556-1.661), p < 0.001) and bradycardia (OR = 1.140 (1.102-1.180), p < 0.001) during the first 10 minutes of respiratory support at birth., Conclusion: During mask ventilation, the median exerted force on a face mask was 297 grams with a maximum of 1455 grams. Higher exerted forces were associated apnoea and bradycardia during the first 10 minutes of respiratory support at birth., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘K.L.A.M. Kuypers is the recipient of an unrestricted research grant from Fisher & Paykel Healthcare Limited; they had no role or influence in study design nor in the collection, analysis, and interpretation of data, writing of the report and decision to submit the paper for publication.’., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The importance of neonatal resuscitator resistance is currently unknown. In this study we investigated peak flows and pressure stability resulting from differences in imposed resistance during positive pressure ventilation(PPV) and simulated spontaneous breathing (SSB) between the r-PAP, low-resistance resuscitator, and Neopuff™, high-resistance resuscitator., Methods: In a bench test, 20 inflations during PPV and 20 breaths during SSB were analysed on breath-by-breath basis to determine peak flow and pressure stability using the Neopuff™ with bias gas flow of 8, 12 or 15 L/min and the r-PAP with total gas flow of 15 L/min., Results: Imposed resistance of the Neopuff™ was significantly reduced when the bias gas flow was increased from 8 to 15 L/min, which resulted in higher peak flows during PPV and SSB. Peak flows in the r-PAP were, however, significantly higher and fluctuations in CPAP during SSB were significantly smaller in the r-PAP compared to the Neopuff™ for all bias gas flow levels. During PPV, a pressure overshoot of 3.2 cmH 2 O was observed in the r-PAP., Conclusions: The r-PAP seemed to have a lower resistance than the Neopuff™ even when bias gas flows were increased. This resulted in more stable CPAP pressures with higher peak flows when using the r-PAP., Impact: The traditional T-piece system (Neopuff™) has a higher imposed resistance compared to a new neonatal resuscitator (r-PAP). This study shows that reducing imposed resistance leads to smaller CPAP fluctuations and higher inspiratory and expiratory peak flows. High peak flows might negatively affect lung function and/or cause lung injury in preterm infants at birth. This study will form the rationale for further studies investigating these effects. A possible compromise might be to use the traditional T-piece system with a higher bias gas flow (12 L/min), thereby reducing the imposed resistance and generating more stable PEEP/CPAP pressures, while limiting potentially harmful peak flows., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)