The effect of vibrotactile stimulation on hypoxia-induced irregular breathing and apnea in preterm rabbits.

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 cmH2O 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.

Occurrence of hyperoxia during iNO treatment for persistent pulmonary hypertension of the newborn: a cohort study.

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 (PaO2) 10-13 kPa and peripheral oxygen saturation (SpO2) 92-98%. The main study outcomes were the incidence and duration of hyperoxemia and hypoxemia and the fraction of inspired oxygen (FiO2). A total of 181 infants were included. The median FiO2 was 0.43 (IQR 0.34-0.56) and the maximum FiO2 was 1.0 in 156/181 (86%) infants, resulting in at least one PaO2 > 13 kPa in 149/181 (82%) infants, of which 46/149 (31%) infants had minimal one PaO2 > 30 kPa. SpO2 was > 98% in 179/181 (99%) infants for 17.7% (8.2-35.6%) of the iNO time. PaO2 < 10 kPa occurred in 160/181 (88%) infants, of which 81/160 (51%) infants had minimal one PaO2 < 6.7 kPa. SpO2 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.

The influence of chorioamnionitis on respiratory drive and spontaneous breathing of premature infants at birth: a narrative review.

Most very premature infants breathe at birth but require respiratory support in order to stimulate and support their breathing. A significant proportion of premature infants are affected by chorioamnionitis, defined as an umbrella term for antenatal inflammation of the foetal membranes and umbilical vessels. Chorioamnionitis produces inflammatory mediators that potentially depress the respiratory drive generated in the brainstem. Such respiratory depression could maintain itself by delaying lung aeration, hampering respiratory support at birth and putting infants at risk of hypoxic injury. This inflammatory-mediated respiratory depression may contribute to an association between chorioamnionitis and increased requirement of neonatal resuscitation in premature infants at birth. This narrative review summarises mechanisms on how respiratory drive and spontaneous breathing could be influenced by chorioamnionitis and provides possible interventions to stimulate spontaneous breathing.  Conclusion: Chorioamnionitis could possibly depress respiratory drive and spontaneous breathing in premature infants at birth. Interventions to stimulate spontaneous breathing could therefore be valuable. What is Known: • A large proportion of premature infants are affected by chorioamnionitis, antenatal inflammation of the foetal membranes and umbilical vessels. What is New: • Premature infants affected by chorioamnionitis might be exposed to higher concentrations of respiratory drive inhibitors which could depress breathing at birth. • Premature infants affected by chorioamnionitis seem to be associated with a higher and more extensive requirement of resuscitation at birth.

Oxygen saturation and heart rate in healthy term and late preterm infants with delayed cord clamping.

Blood oxygen in the fetus is substantially lower than in the newborn infant. In the minutes after birth, arterial oxygen saturation rises from around 50-60% to 90-95%. Initial respiratory efforts generate negative trans-thoracic pressures that drive liquid from the airways into the lung interstitium facilitating lung aeration, blood oxygenation, and pulmonary artery vasodilatation. Consequently, intra- (foramen ovale) and extra-cardiac (ductus arteriosus) shunting changes and the sequential circulation switches to a parallel pulmonary and systemic circulation. Delaying cord clamping preserves blood flow through the ascending vena cava, thus increasing right and left ventricular preload. Recently published reference ranges have suggested that delayed cord clamping positively influenced the fetal-to-neonatal transition. Oxygen saturation in babies with delayed cord clamping plateaus significantly earlier to values of 85-90% than in babies with immediate cord clamping. Delayed cord clamping may also contribute to fewer episodes of brady-or-tachycardia in the first minutes after birth, but data from randomized trials are awaited. IMPACT: Delaying cord clamping during fetal to neonatal transition contributes to a significantly earlier plateauing of oxygen saturation and fewer episodes of brady-and/or-tachycardia in the first minutes after birth. We provide updated information regarding the changes in SpO2 and HR during postnatal adaptation of term and late preterm infants receiving delayed compared with immediate cord clamping. Nomograms in newborn infants with delayed cord clamping will provide valuable reference ranges to establish target SpO2 and HR in the first minutes after birth.

Stimulating and maintaining spontaneous breathing during transition of preterm infants.

Most preterm infants breathe at birth, but need additional respiratory support due to immaturity of the lung and respiratory control mechanisms. To avoid lung injury, the focus of respiratory support has shifted from invasive towards non-invasive ventilation. However, applying effective non-invasive ventilation is difficult due to mask leak and airway obstruction. The larynx has been overlooked as one of the causes for obstruction, preventing face mask ventilation from inflating the lung. The larynx remains mostly closed at birth, only opening briefly during a spontaneous breath. Stimulating and supporting spontaneous breathing could enhance the success of non-invasive ventilation by ensuring that the larynx remains open. Maintaining adequate spontaneous breathing and thereby reducing the need for invasive ventilation is not only important directly after birth, but also in the first hours after admission to the NICU. Respiratory distress syndrome is an important cause of respiratory failure. Traditionally, treatment of RDS required intubation and mechanical ventilation to administer exogenous surfactant. However, new ways have been implemented to administer surfactant and preserve spontaneous breathing while maintaining non-invasive support. In this narrative review we aim to describe interventions focused on stimulation and maintenance of spontaneous breathing of preterm infants in the first hours after birth.

High variability in nurses' tactile stimulation methods in response to apnoea of prematurity-A neonatal manikin study.

AIM: Neonatal intensive care unit (NICU) nurses provide tactile stimulation to terminate apnoea in preterm infants, but guidelines recommending specific methods are lacking. In this study, we evaluated current methods of tactile stimulation performed by NICU nurses. METHODS: Nurses were asked to demonstrate and explain their methods of tactile stimulation on a manikin, using an apnoea scenario. All nurses demonstrated their methods three times in succession, with the manikin positioned either prone, supine or lateral. Finally, the nurses were asked how they decided on the methods of tactile stimulation used. The stimulation methods were logged in chronological order by describing both the technique and the location. The nurses' explanations were transcribed and categorised. RESULTS: In total, 47 nurses demonstrated their methods of stimulation on the manikin. Overall, 57 different combinations of technique and location were identified. While most nurses (40/47, 85%) indicated they learned how to stimulate during their training, 15/40 (38%) of them had adjusted their methods over time. The remaining 7/47 (15%) stated that their stimulation methods were self-developed. CONCLUSION: Tactile stimulation performed by NICU nurses to terminate apnoea was highly variable in both technique and location, and these methods were based on either prior training or intuition.

Caffeine to improve breathing effort of preterm infants at birth: a randomized controlled trial.

BackgroundCaffeine promotes spontaneous breathing by antagonizing adenosine. We assessed the direct effect of caffeine on respiratory effort in preterm infants at birth.MethodsThirty infants of 24-30 weeks of gestation were randomized for receiving caffeine directly after birth in the delivery room (caffeine DR group) or later in the neonatal intensive care unit (control group). Primary outcome was respiratory effort, expressed as minute volume, tidal volumes, respiratory rate, rate of rise to maximum tidal volume, and recruitment breaths at 7-9 min after birth.ResultsAfter correction for gestational age, minute volumes ((mean±SD; 189±74 vs. 162±70 ml/kg/min; P<0.05) and tidal volumes ((median (interquartile range (IQR)) 5.2 (3.9-6.4) vs. 4.4 (3.0-5.6) ml/kg) were significantly greater in the caffeine DR group. Although respiratory rates were similar ((mean±SD) 35±10 vs. 33±10), RoR increased significantly ((median (IQR) 14.3 (11.2-19.8) vs. 11.2 (7.9-15.2) ml/kg/s), and more recruitment breaths were observed (13 vs. 9%).ConclusionCaffeine increases respiratory effort in preterm infants at birth, but the effect on clinical outcomes needs further investigation.

The vocal cords are predominantly closed in preterm infants <30 weeks gestation during transition after birth; an observational study.

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.

Comparison of two different oxygen saturation target ranges for automated oxygen control in preterm infants: a randomised cross-over trial.

OBJECTIVE: To compare the effect of peripheral oxygen saturation (SpO2) 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% (TRlow) or 92%-96% (TRhigh) 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 (SpO2<80% for ≥1 s) and hyperoxic episodes (SpO2>98% for ≥1 s). RESULTS: Hypoxic episodes were less frequent when the higher range was targeted (TRhigh vs TRlow: 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 SpO2 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.

Initial Oxygen Concentration for the Resuscitation of Infants Born at Less Than 32 Weeks' Gestation: A Systematic Review and Individual Participant Data Network Meta-Analysis.

Importance: Resuscitation with lower fractional inspired oxygen (FiO2) reduces mortality in term and near-term infants but the impact of this practice on very preterm infants is unclear. Objective: To evaluate the relative effectiveness of initial FiO2 on reducing mortality, severe morbidities, and oxygen saturations (SpO2) in preterm infants born at less than 32 weeks' gestation using network meta-analysis (NMA) of individual participant data (IPD). Data Sources: MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov, and WHO ICTRP from 1980 to October 10, 2023. Study Selection: Eligible studies were randomized clinical trials enrolling infants born at less than 32 weeks' gestation comparing at least 2 initial oxygen concentrations for delivery room resuscitation, defined as either low (≤0.3), intermediate (0.5-0.65), or high (≥0.90) FiO2. Data Extraction and Synthesis: Investigators from eligible studies were invited to provide IPD. Data were processed and checked for quality and integrity. One-stage contrast-based bayesian IPD-NMA was performed with noninformative priors and random effects and adjusted for key covariates. Main Outcomes and Measures: The primary outcome was all-cause mortality at hospital discharge. Secondary outcomes were morbidities of prematurity and SpO2 at 5 minutes. Results: IPD were provided for 1055 infants from 12 of the 13 eligible studies (2005-2019). Resuscitation with high (≥0.90) initial FiO2 was associated with significantly reduced mortality compared to low (≤0.3) (odds ratio [OR], 0.45; 95% credible interval [CrI], 0.23-0.86; low certainty) and intermediate (0.5-0.65) FiO2 (OR, 0.34; 95% CrI, 0.11-0.99; very low certainty). High initial FiO2 had a 97% probability of ranking first to reduce mortality. The effects on other morbidities were inconclusive. Conclusions and Relevance: High initial FiO2 (≥0.90) may be associated with reduced mortality in preterm infants born at less than 32 weeks' gestation compared to low initial FiO2 (low certainty). High initial FiO2 is possibly associated with reduced mortality compared to intermediate initial FiO2 (very low certainty) but more evidence is required.

Future of clinical trials in the delivery room: time for pragmatism.

Despite increased amounts of research, most of the evidence that supports treatment of newborns in the delivery room is rated 'low' rather than 'high' quality. This assessment stems largely from a lack of evidence from clinical trials. When trials have been performed, the evidence has often been downgraded due to enrolment of small or poorly representative samples, and for lack of blinding of caregivers and outcome assessors. Delivery room trials present particular challenges when obtaining consent, enrolling participants, taking measures to limit bias and identifying appropriate outcome measures. We hope our suggestions as to how future delivery room trials could be more pragmatic will inform the design of large studies that are necessary to allow clinical practice to evolve.

Comparison of two automated oxygen controllers in oxygen targeting in preterm infants during admission: an observational study.

OBJECTIVE: To compare the effect of two different automated oxygen control devices on time preterm infants spent in different oxygen saturation (SpO2) ranges during their entire stay in the neonatal intensive care unit (NICU). DESIGN: Retrospective cohort study of prospectively collected data. SETTING: Tertiary level neonatal unit in the Netherlands. PATIENTS: Preterm infants (OxyGenie 75 infants, CLiO2 111 infants) born at 24-29 weeks' gestation receiving at least 72 hours of respiratory support between October 2015 and November 2020. INTERVENTIONS: Inspired oxygen concentration was titrated by the OxyGenie controller (SLE6000 ventilator) between February 2019 and November 2020 and the CLiO2 controller (AVEA ventilator) between October 2015 and December 2018 as standard of care. MAIN OUTCOME MEASURES: Time spent within SpO2 target range (TR, 91-95% for either epoch) and other SpO2 ranges. RESULTS: Time spent within the SpO2 TR when receiving supplemental oxygen was higher during OxyGenie control (median 71.5 [IQR 64.6-77.0]% vs 51.3 [47.3-58.5]%, p<0.001). Infants under OxyGenie control spent less time in hypoxic and hyperoxic ranges (SpO2<80%: 0.7 [0.4-1.4]% vs 1.2 [0.7-2.3]%, p<0.001; SpO2>98%: 1.0 [0.5-2.4]% vs 4.0 [2.0-7.9]%, p<0.001). Both groups received a similar FiO2 (29.5 [28.0-33.2]% vs 29.6 [27.7-32.1]%, p=not significant). CONCLUSIONS: Oxygen saturation targeting was significantly different in the OxyGenie epoch in preterm infants, with less time in hypoxic and hyperoxic SpO2 ranges during their stay in the NICU.

Assessment of Comfort during Less Invasive Surfactant Administration in Very Preterm Infants: A Multicenter Study.

INTRODUCTION: This study was set up to investigate if and to what extent non-pharmacological analgesia is able to provide comfort to very preterm infants (VPI) during less invasive surfactant administration (LISA). METHODS: This was a prospective non-randomized multicenter observational study performed in level IV NICUs. Inborn VPI with a gestational age between 220/7 and 316/7 weeks, signs of respiratory distress syndrome, and the need for surfactant replacement were included. Non-pharmacological analgesia was performed in all infants during LISA. In case of failure of the first LISA attempt, additional analgosedation could be administered. COMFORTneo scores during LISA were assessed. RESULTS: 113 VPI with a mean gestational age of 27 weeks (+/- 2.3 weeks) and mean birth weight of 946 g (+/- 33 g) were included. LISA was successful at the first laryngoscopy attempt in 81%. COMFORTneo scores were highest during laryngoscopy. At this time point, non-pharmacological analgesia provided adequate comfort in 61% of the infants. 74.4% of lower gestational aged infants (i.e., 220-266 weeks) were within the comfort zone during laryngoscopy compared to 51.6% of higher gestational aged infants (i.e., 270-320 weeks) (p = 0.016). The time point of surfactant administration did not influence the COMFORTneo scores during the LISA procedure. CONCLUSION: Non-pharmacological analgesia provided comfort in as much as 61% of the included VPI during LISA. Further research is needed to both develop strategies to identify infants who, despite receiving non-pharmacological analgesia, are at high risk for experiencing discomfort during LISA and define patient-tailored dosage and choice of analgosedative drugs.

Effect of initial and subsequent mask applications on breathing and heart rate in preterm infants at birth.

OBJECTIVE: Application of a face mask may provoke the trigeminocardiac reflex, leading to apnoea and bradycardia. This study investigates whether re-application of a face mask in preterm infants at birth alters the risk of apnoea compared with the initial application, and identify factors that influence this risk. METHODS: Resuscitation videos and respiratory function monitor data collected from preterm infants <30 weeks gestation between 2018 and 2020 were reviewed. Breathing and heart rate before and after the initial and subsequent mask applications were analysed. RESULTS: In total, 111 infants were included with 404 mask applications (102 initial and 302 subsequent mask applications). In 254/404 (63%) applications, infants were breathing prior to mask application, followed by apnoea after 67/254 (26%) mask applications. Apnoea and bradycardia occurred significantly more often after the initial mask application compared with subsequent applications (apnoea initial: 32/67 (48%) and subsequent: 44/187 (24%), p<0.001; bradycardia initial: 61% and subsequent 21%, p<0.001). Apnoea was followed by bradycardia in 73% and 71% of the initial and subsequent mask applications, respectively (p=0.607).In a logistic regression model, a lower breathing rate (OR 0.908 (95% CI 0.847 to 0.974), p=0.007) and heart rate (OR 0.935 (95% CI 0.901 to 0.970), p<0.001) prior to mask application were associated with an increased likelihood of becoming apnoeic following subsequent mask applications. CONCLUSION: In preterm infants at birth, apnoea and bradycardia occurs more often after an initial mask application than subsequent applications, with lower heart and breathing rates increasing the risk of apnoea in subsequent applications.

Comparing Descriptive Statistics for Retrospective Studies From One-per-Minute and One-per-Second Data.

Background: Large amounts of data are collected in neonatal intensive care units, which could be used for research. It is unclear whether these data, usually sampled at a lower frequency, are sufficient for retrospective studies. We investigated what to expect when using one-per-minute data for descriptive statistics. Methods: One-per-second inspiratory oxygen and saturation were processed to one-per-minute data and compared, on average, standard deviation, target range time, hypoxia, days of supplemental oxygen, and missing signal. Results: Outcomes calculated from data recordings (one-per-minute = 92, one-per-second = 92) showed very little to no difference. Sub analyses of recordings under 100 and 200 h showed no difference. Conclusion: In our study, descriptive statistics of one-per-minute data were comparable to one-per-second and could be used for retrospective analyses. Comparable routinely collected one-per-minute data could be used to develop algorithms or find associations, retrospectively.

Technology in the delivery room supporting the neonatal healthcare provider's task.

Very preterm infants are a unique and highly vulnerable group of patients that have a narrow physiological margin within which interventions are safe and effective. The increased understanding of the foetal to neonatal transition marks the intricacy of the rapid and major physiological changes that take place, making delivery room stabilisation and resuscitation an increasingly complex and sophisticated activity for caregivers to perform. While modern, automated technologies are progressively implemented in the neonatal intensive care unit (NICU) to enhance the caregivers in providing the right care for these patients, the technology in the delivery room still lags far behind. Diligent translation of well-known and promising technological solutions from the NICU to the delivery room will allow for better support of the caregivers in performing their tasks. In this review we will discuss the current technology used for stabilisation of preterm infants in the delivery room and how this could be optimised in order to further improve care and outcomes of preterm infants in the near future.

NETwork Meta-analysis Of Trials of Initial Oxygen in preterm Newborns (NETMOTION): A Protocol for Systematic Review and Individual Participant Data Network Meta-Analysis of Preterm Infants <32 Weeks' Gestation Randomized to Initial Oxygen Concentration for Resuscitation.

BACKGROUND: Internationally recognized guidelines recommend the judicious use of low oxygen (21-30%), titrated to peripheral oxygen saturation targets, for the initiation of resuscitation of very and extremely preterm infants (<32 weeks' gestation). However, despite more than 10 randomized controlled trials on this question, the ideal initial oxygen concentration for this group of vulnerable infants remains uncertain. AIMS: This study aims to assess the effect of various initial oxygen concentrations on (1) all-cause mortality, chronic lung disease, intraventricular hemorrhage, and retinopathy of prematurity; and (2) reaching the prescribed oxygen saturation targets by 5 min after birth, in preterm infants requiring resuscitation. METHODS: We will conduct a systematic review and network meta-analysis using individual participant data. Studies of preterm infants <32 weeks' gestation, randomized to initial oxygen concentration, will be included. We will systematically search medical databases and trial registries for eligible studies (published or unpublished). Records will be screened by two independent reviewers, with conflicts resolved by the inclusion of a third reviewer. Identified initial oxygen concentrations will be grouped into the following nodes: low (≤30%), intermediate (60%), and high (≥90%) oxygen. A two-step random-effects contrast-based network meta-regression will be calculated to compare and rank different oxygen concentrations. Analyses will be intention-to-treat, with the primary outcome of all-cause mortality. DISCUSSION: This is the first individual participant data network meta-analysis of initial oxygen concentrations for the resuscitation of preterm infants. This novel approach may address long-standing uncertainty regarding optimal oxygen supplementation practice for the resuscitation of preterm infants <32 weeks' gestation.

Feasibility and Effect of Physiological-Based CPAP in Preterm Infants at Birth.

Background: Preterm infants are commonly supported with 5-8 cmH2O CPAP. However, animal studies demonstrate that high initial CPAP levels (12-15 cmH2O) which are then reduced (termed physiological based (PB)-CPAP), improve lung aeration without adversely affecting cardiovascular function. We investigated the feasibility of PB-CPAP and the effect in preterm infants at birth. Methods: Preterm infants (24-30 weeks gestation) were randomized to PB-CPAP or 5-8 cmH2O CPAP for the first 10 min after birth. PB-CPAP consisted of 15 cmH2O CPAP that was decreased when infants were stabilized (heart rate ≥100 bpm, SpO2 ≥85%, FiO2 ≤ 0.4, spontaneous breathing) to 8 cmH2O with steps of ~2/3 cmH2O/min. Primary outcomes were feasibility and SpO2 in the first 5 min after birth. Secondary outcomes included physiological and breathing parameters and short-term neonatal outcomes. Planned enrollment was 42 infants. Results: The trial was stopped after enrolling 31 infants due to a low inclusion rate and recent changes in the local resuscitation guideline that conflict with the study protocol. Measurements were available for analysis in 28 infants (PB-CPAP n = 8, 5-8 cmH2O n = 20). Protocol deviations in the PB-CPAP group included one infant receiving 3 inflations with 15 cmH2O PEEP and two infants in which CPAP levels were decreased faster than described in the study protocol. In the 5-8 cmH2O CPAP group, three infants received 4, 10, and 12 cmH2O CPAP. During evaluations, caregivers indicated that the current PB-CPAP protocol was difficult to execute. The SpO2 in the first 5 min after birth was not different [61 (49-70) vs. 64 (47-74), p = 0.973]. However, infants receiving PB-CPAP achieved higher heart rates [121 (111-130) vs. 97 (82-119) bpm, p = 0.016] and duration of mask ventilation was shorter [0:42 (0:34-2:22) vs. 2:58 (1:36-6:03) min, p = 0.020]. Infants in the PB-CPAP group required 6:36 (5:49-11:03) min to stabilize, compared to 9:57 (6:58-15:06) min in the 5-8 cmH2O CPAP group (p = 0.256). There were no differences in short-term outcomes. Conclusion: Stabilization of preterm infants with PB-CPAP is feasible but tailoring CPAP appeared challenging. PB-CPAP did not lead to higher SpO2 but increased heart rate and shortened the duration of mask ventilation, which may reflect faster lung aeration.

The Effect of Initial Oxygen Exposure on Diaphragm Activity in Preterm Infants at Birth.

Background: The initial FiO2 that should be used for the stabilization of preterm infants in the delivery room (DR) is still a matter of debate as both hypoxia and hyperoxia should be prevented. A recent randomized controlled trial showed that preterm infants [gestational age (GA) < 30 weeks] stabilized with an initial high FiO2 (1.0) had a significantly higher breathing effort than infants stabilized with a low FiO2 (0.3). As the diaphragm is the main respiratory muscle in these infants, we aimed to describe the effects of the initial FiO2 on diaphragm activity. Methods: In a subgroup of infants from the original bi-center randomized controlled trial diaphragm activity was measured with transcutaneous electromyography of the diaphragm (dEMG), using three skin electrodes that were placed directly after birth. Diaphragm activity was compared in the first 5 min after birth. From the dEMG respiratory waveform several outcome measures were determined for comparison of the groups: average peak- and tonic inspiratory activity (dEMGpeak and dEMGton, respectively), inspiratory amplitude (dEMGamp), area under the curve (dEMGAUC) and the respiratory rate (RR). Results: Thirty-one infants were included in this subgroup, of which 29 could be analyzed [n = 15 (median GA 28.4 weeks) and n = 14 (median GA 27.9 weeks) for the 100 and 30% oxygen group, respectively]. Tonic diaphragm activity was significantly higher in the high FiO2-group (4.3 ± 2.1 µV vs. 2.9 ± 1.1 µV; p = 0.047). The other dEMG-parameters (dEMGpeak, dEMGamp, dEMGAUC) showed consistently higher values in the high FiO2 group, but did not reach statistical significance. Average RR showed similar values in both groups (34 ± 9 vs. 32 ± 10 breaths/min for the high and low oxygen group, respectively). Conclusion: Preterm infants stabilized with an initial high FiO2 showed significantly more tonic diaphragm activity and an overall trend toward a higher level of diaphragm activity than those stabilized with an initial low FiO2. These results confirm that a high initial FiO2 after birth stimulates breathing effort, which can be objectified with dEMG.