Deciphering Mechanisms of Respiratory Fetal-to-Neonatal Transition in Very Preterm Infants.

Rationale: The respiratory mechanisms of a successful transition of preterm infants after birth are largely unknown. Objectives: To describe intrapulmonary gas flows during different breathing patterns directly after birth. Methods: Analysis of electrical impedance tomography data from a previous randomized trial in preterm infants at 26-32 weeks gestational age. Electrical impedance tomography data for individual breaths were extracted, and lung volumes as well as ventilation distribution were calculated for end of inspiration, end of expiratory braking and/or holding maneuver, and end of expiration. Measurements and Main Results: Overall, 10,348 breaths from 33 infants were analyzed. We identified three distinct breath types within the first 10 minutes after birth: tidal breathing (44% of all breaths; sinusoidal breathing without expiratory disruption), braking (50%; expiratory brake with a short duration), and holding (6%; expiratory brake with a long duration). Only after holding breaths did end-expiratory lung volume increase: Median (interquartile range [IQR]) = 2.0 AU/kg (0.6 to 4.3), 0.0 (-1.0 to 1.1), and 0.0 (-1.1 to 0.4), respectively; P < 0.001]. This was mediated by intrathoracic air redistribution to the left and non-gravity-dependent parts of the lung through pendelluft gas flows during braking and/or holding maneuvers. Conclusions: Respiratory transition in preterm infants is characterized by unique breathing patterns. Holding breaths contribute to early lung aeration after birth in preterm infants. This is facilitated by air redistribution during braking/holding maneuvers through pendelluft flow, which may prevent lung liquid reflux in this highly adaptive situation. This study deciphers mechanisms for a successful fetal-to-neonatal transition and increases our pathophysiological understanding of this unique moment in life. Clinical trial registered with www.clinicaltrials.gov (NCT04315636).

Rescue nasopharyngeal tube for preterm infants non-responsive to initial ventilation after birth.

BACKGROUND: Physiological changes during the insertion of a rescue nasopharyngeal tube (NPT) after birth are unclear. METHODS: Observational study of very preterm infants in the delivery room. Data were extracted at predefined timepoints starting with first facemask placement after birth until 5 min after insertion of NPT. End-expiratory lung impedance (EELI), heart rate (HR) and SpO2/FiO2-ratio were analysed over time. Changes during the same time span of NIPPV via facemask and NIPPV via NPT were compared. RESULTS: Overall, 1154 inflations in 15 infants were analysed. After NPT insertion, EELI increased significantly [0.33 AU/kg (0.19-0.57), p < 0.001]. Compared with the mask period, changes in EELI were not significantly larger during the NPT period [median difference (IQR) = 0.14 AU/kg (-0.14-0.53); p = 0.12]. Insertion of the NPT was associated with significant improvement in HR [52 (33-96); p = 0.001] and SpO2/FiO2-ratio [161 (69-169); p < 0.001] not observed during the mask period. CONCLUSIONS: In very preterm infants non-responsive to initial facemask ventilation after birth, insertion of an NPT resulted in a considerable increase in EELI. This additional gain in lung volume was associated with an immediate improvement in clinical parameters. The use of a NPT may prevent intubation in selected non-responsive infants. IMPACT: After birth, a nasopharyngeal tube may be considered as a rescue airway in newborn infants non-responsive to initial positive pressure ventilation via facemask. Although it is widely used among clinicians, its effect on lung volumes and physiological parameters remains unclear. Insertion of a rescue NPT resulted in a considerable increase in lung volume but this was not significantly larger than during facemask ventilation. However, insertion of a rescue NPT was associated with a significant and clinically important improvement in heart rate and oxygenation. This study highlights the importance of individual strategies in preterm resuscitation and introduces the NPT as a valid option.

The DELUX study: development of lung volumes during extubation of preterm infants.

OBJECTIVE: To measure changes in end-expiratory lung impedance (EELI) as a marker of functional residual capacity (FRC) during the entire extubation procedure of very preterm infants. METHODS: Prospective observational study in preterm infants born at 26-32 weeks gestation being extubated to non-invasive respiratory support. Changes in EELI and cardiorespiratory parameters (heart rate, oxygen saturation) were recorded at pre-specified events during the extubation procedure compared to baseline (before first handling of the infant). RESULTS: Overall, 2912 breaths were analysed in 12 infants. There was a global change in EELI during the extubation procedure (p = 0.029). EELI was lowest at the time of extubation [median (IQR) difference to baseline: -0.30 AU/kg (-0.46; -0.14), corresponding to an FRC loss of 10.2 ml/kg (4.8; 15.9), padj = 0.004]. The biggest EELI loss occurred during adhesive tape removal [median change (IQR): -0.18 AU/kg (-0.22; -0.07), padj = 0.004]. EELI changes were highly correlated with changes in the SpO2/FiO2 ratio (r = 0.48, p < 0.001). Forty per cent of FRC was re-recruited at the tenth breath after the initiation of non-invasive ventilation (p < 0.001). CONCLUSIONS: The extubation procedure is associated with significant changes in FRC. This study provides novel information for determining the optimal way of extubating a preterm infant. IMPACT: This study is the first to examine the development of lung volumes during the entire extubation procedure including the impact of associated events. The extubation procedure significantly affects functional residual capacity with a loss of approximately 10 ml/kg at the time of extubation. Removal of adhesive tape is the major contributing factor to FRC loss during the extubation procedure. Functional residual capacity is regained within the first breaths after initiation of non-invasive ventilation and is further increased after turning the infant into the prone position.

"Harry Potter and the Multitudinous Maladies": a retrospective population-based observational study of morbidity and mortality among witches and wizards.

OBJECTIVES: To describe the prevalence of maladies and deaths among witches and wizards in the Harry Potter world, their causes, and associated therapies. DESIGN: Retrospective population-based observational study (report analysis) undertaken 10 February - 19 March 2022. SETTING: All locations described in the Harry Potter books, predominantly Hogwarts School of Witchcraft and Wizardry, but also selected locations, including Privet Drive No 4, Diagon Alley, the Ministry of Magic, and The Burrow. PARTICIPANTS: All witches and wizards mentioned at least once in any of the seven Harry Potter books. MAIN OUTCOME MEASURES: Overall numbers of maladies and deaths. Secondary outcomes were changes in morbidity and mortality over time, causes of morbidity and mortality, and treatments. RESULTS: A total of 603 wizards or witches named in the Potter books experienced 1541 maladies and injuries (1410 non-fatal) and 131 deaths. Overall morbidity incidence was 471 events per 1000 individuals, and mortality, after adjustment for Lord Voldemort's multi-mortality, was 20.6%. The most frequent causes of morbidity were traumatic injuries during duels or fights (553 cases, 39.2%), magical objects, potions, plants, or creatures (345, 24.5%), and non-combative trauma (221, 15.7%). Most deaths were related to wizarding duels (101 of 131, 77.1%). Treatments were rarely described; the most frequent were jinxes (274, 19.4%) and potions (136, 9.6%). Hospital stays were shorter than a week for almost all non-fatal maladies (1397 of 1410, 99.1%). CONCLUSIONS: Morbidity and, in particular, mortality were very high and predominantly caused by magical means. Further investigation into the safety at Hogwarts School of Witchcraft and Wizardry is warranted. The few treatments used had high success rates; rapid recovery was the rule, and hospital stays generally brief. Efforts should be undertaken to identify the magical therapies and interventions used and to introduce these novel remedies into Muggle medicine.

Transmission of Oscillatory Volumes into the Preterm Lung during Noninvasive High-Frequency Ventilation.

Rationale: There is increasing evidence for a clinical benefit of noninvasive high-frequency oscillatory ventilation (nHFOV) in preterm infants. However, it is still unknown whether the generated oscillations are effectively transmitted to the alveoli.Objectives: To assess magnitude and regional distribution of oscillatory volumes (VOsc) at the lung level.Methods: In 30 prone preterm infants enrolled in a randomized crossover trial comparing nHFOV with nasal continuous positive airway pressure, electrical impedance tomography recordings were performed. During nHFOV, the smallest amplitude to achieve visible chest wall vibration was used, and the frequency was set at 8 hertz.Measurements and Main Results: Thirty consecutive breaths during artifact-free tidal ventilation were extracted for each of the 228 electrical impedance tomography recordings. After application of corresponding frequency filters, Vt and VOsc were calculated. There was a signal at 8 and 16 Hz during nHFOV, which was not detectable during nasal continuous positive airway pressure, corresponding to the set oscillatory frequency and its second harmonic. During nHFOV, the mean (SD) VOsc/Vt ratio was 0.20 (0.13). Oscillations were more likely to be transmitted to the non-gravity-dependent (mean difference [95% confidence interval], 0.041 [0.025-0.058]; P < 0.001) and right-sided lung (mean difference [95% confidence interval], 0.040 [0.019-0.061]; P < 0.001) when compared with spontaneous Vt.Conclusions: In preterm infants, VOsc during nHFOV are transmitted to the lung. Compared with the regional distribution of tidal breaths, oscillations preferentially reach the right and non-gravity-dependent lung. These data increase our understanding of the physiological processes underpinning nHFOV and may lead to further refinement of this novel technique.

Tidal volumes during delivery room stabilization of (near) term infants.

BACKGROUND: We sought to assess tidal volumes in (near) term infants during delivery room stabilization. METHODS: Secondary analysis of a prospective study comparing two facemasks used for positive pressure ventilation (PPV) in newborn infants ≥ 34 weeks gestation. PPV was provided with a T-piece device with a PIP of 30 cmH2O and positive end-expiratory airway pressure of 5 cmH2O. Expired tidal volumes (Vt) were measured with a respiratory function monitor. Target range for Vt was defined to be 4 - 8 ml/kg. RESULTS: Twenty-three infants with a median (IQR) gestational age of 38.1 (36.4 - 39.0) weeks received 1828 inflations with a median Vt of 4.6 (3.3 - 6.2) ml/kg. Median Vt was in the target range in 12 infants (52%), lower in 9 (39%) and higher in 2 (9%). Thirty-six (25-27) % of the inflations were in the target rage over the duration of PPV while 42 (25 - 65) % and 10 (3 - 33) % were above and below target range. CONCLUSIONS: Variability of expiratory tidal volume delivered to term and late preterm infants was wide. Reliance on standard pressures and clinical signs may be insufficient to provide safe and effective ventilation in the delivery room. TRIAL REGISTRATION: This is a secondary analysis of a prospectively registered randomized controlled trial (ACTRN12616000768493).

The Effect of Noninvasive High-Frequency Oscillatory Ventilation on Desaturations and Bradycardia in Very Preterm Infants: A Randomized Crossover Trial.

Noninvasive high-frequency oscillatory ventilation compared with nasal continuous positive airway pressure significantly reduced the number of desaturations and bradycardia in preterm infants. However, noninvasive high-frequency oscillatory ventilation was associated with increased oxygen requirements and higher heart rates. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry: ACTRN12616001516471.

Suction Mask vs Conventional Mask Ventilation in Term and Near-Term Infants in the Delivery Room: A Randomized Controlled Trial.

OBJECTIVE: To compare the suction mask, a new facemask that uses suction to create a seal between the mask and the infant's face, with a conventional soft, round silicone mask during positive pressure ventilation (PPV) in the delivery room in newborn infants >34 weeks of gestation. STUDY DESIGN: Single-center randomized controlled trial in the delivery room. The primary outcome was mask leak. RESULTS: Forty-five infants were studied at a median gestational age of 38.1 weeks (IQR, 36.4-39.0 weeks); 22 were randomized to the suction mask and 23 to the conventional mask. The suction mask did not reduce mask leak (49.9%; IQR, 11.0%-92.7%) compared with the conventional mask (30.5%; IQR, 10.6%-48.8%; P = .51). The suction mask delivered lower peak inspiratory pressure (27.2 cm H2O [IQR, 25.0-28.7 cm H2O] vs 30.4 cm H2O [IQR, 29.4-32.5 cm H2O]; P < .05) and lower positive end expiratory pressure (3.7 cm H2O [IQR, 3.1-4.5 cm H2O] vs 5.1 cm H2O [IQR, 4.2-5.7 cm H2O ]; P < .05). There was no difference in the duration of PPV or rates of intubation or admission to the neonatal intensive care unit. In 5 infants (23%), the clinician switched from the suction to the conventional mask, 2 owing to intermittently low peak inspiratory pressure, 2 owing to failure to respond to PPV, and 1 owing to marked facial bruising after 6 minutes of PPV. CONCLUSIONS: The use of the suction mask to provide PPV in newborn infants did not reduce facemask leak. Adverse effects such as the inability to achieve the set pressures and transient skin discoloration are concerning. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry ACTRN12616000768493.

Xenon as an adjuvant to therapeutic hypothermia in near-term and term newborns with hypoxic-ischaemic encephalopathy.

BACKGROUND: Hypoxic-ischaemic encephalopathy (HIE) is a serious birth complication affecting term and late preterm newborns. Although therapeutic hypothermia (cooling) has been shown to be an effective therapy for neonatal HIE, many cooled infants have poor long-term neurodevelopmental outcomes. In animal models of neonatal encephalopathy, inhaled xenon combined with cooling has been shown to offer better neuroprotection than cooling alone. OBJECTIVES: To determine the effects of xenon as an adjuvant to therapeutic hypothermia on mortality and neurodevelopmental morbidity, and to ascertain clinically important side effects of xenon plus therapeutic hypothermia in newborn infants with HIE. To assess early predictors of adverse outcomes and potential side effects of xenon. SEARCH METHODS: We used the standard strategy of the Cochrane Neonatal Review Group to search the Cochrane Library (2017, Issue 8), MEDLINE (from 1966), Embase (from 1966), and PubMed (from 1966) for randomised controlled and quasi-randomised trials. We also searched conference proceedings and the reference lists of cited articles. We conducted our most recent search in August 2017. SELECTION CRITERIA: We included all trials allocating term or late preterm encephalopathic newborns to cooling plus xenon or cooling alone, irrespective of timing (starting age and duration) and concentrations used for xenon administration. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed results of searches against predetermined criteria for inclusion, assessed risk of bias, and extracted data. We performed meta-analyses using risk ratios (RRs), risk differences (RDs), and number needed to treat for an additional beneficial outcome (NNTB) with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences (MDs) for continuous data. MAIN RESULTS: A single randomised controlled trial enrolling 92 participants was eligible for this review. Researchers have not reported long-term neurodevelopmental outcomes, including the primary outcome of this review - death or long-term major neurodevelopmental disability in infancy (18 months to three years of age). Cooling plus xenon was not associated with reduced mortality at latest follow-up, based upon low quality evidence. Investigators noted no substantial differences between groups for other secondary outcomes of this review, such as biomarkers of brain damage assessed with magnetic resonance imaging and occurrence of seizures during primary hospitalisation. Available data do not show an increased adverse event rate in the cooling plus xenon group compared with the cooling alone group. AUTHORS' CONCLUSIONS: Current evidence from one small randomised controlled pilot trial is inadequate to show whether cooling plus xenon is safe or effective in near-term and term newborns with HIE. Further trials reporting long-term neurodevelopmental outcomes are needed.

The Pediatric Index of Mortality as a Trigger Tool for the Detection of Serious Errors and Adverse Events.

OBJECTIVES: To test the hypothesis that patients who die in a PICU despite a low predicted mortality at PICU admission are affected by serious errors and adverse events. DESIGN: Retrospective cross-sectional review of medical records for serious errors and adverse events. SETTING: Tertiary interdisciplinary neonatal PICU. PATIENTS: All admissions to our PICU who died despite a low expected mortality (Pediatric Index of Mortality) of less than 10% (trigger-positive admissions). They were compared with a random sample of 100 PICU admissions with a Pediatric Index of Mortality of less than 10% who survived (trigger-negative admissions). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 7,383 admissions (91%) with a Pediatric Index of Mortality 2 below 10%. Seventy-two trigger-positive admissions and 100 trigger-negative admissions met the criteria for detailed chart review. Forty-five serious errors and adverse events were identified, 0.47 per trigger-positive admission and 0.11 per trigger-negative admission (p < 0.001). Nineteen serious errors and adverse events (42%) were related to clinical sepsis acquired during the PICU stay, 17 (89%) in trigger-positive admissions and two (11%) in trigger-negative admissions (p < 0.001). A further 18 serious errors and adverse events (40%) were intervention related, nine (50%) in trigger-positive admissions and nine (50%) in trigger-negative admissions (p = 0.46). Eight serious errors and adverse events (18%) were associated with medication use, all of which occurred in trigger-positive admissions (p = 0.001). The median (interquartile range) age for admissions with and without serious errors and adverse events was 0.3 months (0.0-4.6 mo) and 7.4 months (0.4-58.4 mo) (p < 0.001), and their median (interquartile range) duration of invasive ventilation was 140 hours (50-451 hr) and 2 hours (0-41 hr) (p < 0.001), respectively. CONCLUSIONS: The records of PICU patients with a low expected mortality at admission and death in PICU should be reviewed routinely and/or discussed at morbidity and mortality meetings. These patients may have experienced more in-hospital safety-related events compared with PICU patients with a low Pediatric Index of Mortality who survived. Such adverse events may be amenable to system changes, thus improving patient care.

Nonpublication and discontinuation of randomised controlled trials in newborns.

AIM: To determine the rate of nonpublication and discontinuation of randomised controlled trials (RCTs) in newborns. METHODS: This was a retrospective, cross-sectional study of RCTs registered with the Australian and New Zealand Clinical Trials Registry (ANZCTR) between 2008 and 2012. RESULTS: Fifty trials were identified, of which 23 (46%) were retrospectively registered. Thirty trials (60%) were published. After a median follow-up of 8.0 (range 4.6-17.4) years from Research Ethics Committee approval, 15 of 41 completed trials (37%) remained unpublished, representing 5422 neonatal trial participants. Nine trials (18%) were discontinued, including four that were published. The most frequent reason for discontinuation was poor recruitment (n = 4). Sample size discrepancies between registration and publication were found in 17 (65%) of the 26 completed, published trials. In nine (35%) of these trials, the calculated sample size in the method section of the published article differed from the planned sample size in the trial registry (relative difference -20% to +33%). CONCLUSION: Nonpublication and discontinuation of RCTs conducted in newborns is common. Additional efforts are needed to minimise the number of neonatal trial participants that are exposed to interventions without subsequent publication.

Minimally invasive, imaging guided virtual autopsy compared to conventional autopsy in foetal, newborn and infant cases: study protocol for the paediatric virtual autopsy trial.

BACKGROUND: In light of declining autopsy rates around the world, post-mortem MR imaging is a promising alternative to conventional autopsy in the investigation of infant death. A major drawback of this non-invasive autopsy approach is the fact that histopathological and microbiological examination of the tissue is not possible. The objective of this prospective study is to compare the performance of minimally invasive, virtual autopsy, including CT-guided biopsy, with conventional autopsy procedures in a paediatric population. METHODS/DESIGN: Foetuses, newborns and infants that are referred for autopsy at three different institutions associated with the University of Zurich will be eligible for recruitment. All bodies will be examined with a commercial CT and a 3 Tesla MRI scanner, masked to the results of conventional autopsy. After cross-sectional imaging, CT-guided tissue sampling will be performed by a multifunctional robotic system (Virtobot) allowing for automated post-mortem biopsies. Virtual autopsy results will be classified with regards to the likely final diagnosis and major pathological findings and compared to the results of conventional autopsy, which remains the diagnostic gold standard. DISCUSSION: There is an urgent need for the development of alternative post-mortem examination methods, not only as a counselling tool for families and as a quality control measure for clinical diagnosis and treatment but also as an instrument to advance medical knowledge and clinical practice. This interdisciplinary study will determine whether virtual autopsy will narrow the gap in information between non-invasive and traditional autopsy procedures. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01888380.

Analgosedation for less-invasive surfactant administration: Variations in practice.

BACKGROUND: Less-invasive surfactant administration (LISA) is widely used for surfactant delivery to spontaneously breathing preterm infants on nasal CPAP. However, the use of analgesia and/or sedation for the LISA procedure remains controversial. METHODS: We conducted a cross-sectional survey of all tertiary neonatal intensive care units (NICUs) in Austria, Germany, and Switzerland to assess current practices of analgosedation for LISA in preterm infants. RESULTS: Eighty-eight of 172 (51.2%) NICUs responded to the survey, of which 83 (94.3%) perform LISA. Analgosedation for LISA is used in 60 (72.3%) NICUs. Twenty-eight of those (46.7%) have unit protocols to guide analgosedation while 32 (53.3%) administer medication at the discretion of the attending physician. Ketamine (45.0% of NICUs), propofol (41.7%), fentanyl (21.7%), morphine (20.0%), and midazolam (20.0%) were most frequently used for analgosedation for LISA. Nine (10.7%) NICUs reported the use of pain or distress scores during LISA. CONCLUSION: LISA is well established among tertiary NICUs in the German-speaking countries. However, there are considerable variations regarding the use of analgosedation. More evidence is required to guide clinicians seeking to safely and effectively deliver surfactant via a thin catheter to spontaneously breathing preterm infants.

Nasal high frequency oscillatory highflow therapy in preterm infants: A randomized crossover trial.

OBJECTIVES: To assess the clinical efficacy, safety, and potential physiological mechanisms of highflow therapy with superimposed high frequency oscillations ("osciflow"). STUDY DESIGN: In this prospective, randomized, single center crossover trial, 30 preterm infants were randomized to receive osciflow or highflow therapy first, each for 180 min. During osciflow, an oscillatory amplitude of 20 mbar and a frequency of 6 Hz were set. The flow rate was 4 L/min during both interventions. Primary outcome was the paired difference in the combined number of desaturations (SpO2 < 80%) and bradycardia (heart rate <80 beats per min) between interventions. Safety outcomes included nasal trauma, pneumothorax and treatment failure, and a pain score was assessed. In 20 infants, electrical impedance tomography (EIT) recordings were performed to evaluate oscillatory (VOsc ) and tidal volumes (VT ) at the lung level. RESULTS: Infants with a mean (SD) postnatal age of 33.1 ± 1.2 weeks were included. The median (IQR) number of episodes of desaturation and bradycardia was 19.5 (6-49) during osciflow and 26 (6-44) during highflow therapy (paired difference -2; IQR -10 to 9; p = .37). There were no differences in safety outcomes and pain scores. During osciflow, EIT recordings showed a signal at 6 Hz, which was not detectable during highflow. Corresponding mean (SD) VOsc /VT ratio was 9% (±5%). CONCLUSIONS: In preterm infants, osciflow did not reduce the number of desaturations and bradycardia compared with highflow therapy. Although VOsc were transmitted to the lung during osciflow, their magnitude was small. Osciflow was safe and well tolerated.

Simultaneous atelectasis in human bocavirus infected monozygotic twins: was it plastic bronchitis?

BACKGROUND: Plastic bronchitis is an extremely rare disease characterized by the formation of tracheobronchial airway casts, which are composed of a fibrinous exudate with rubber-like consistency and cause respiratory distress as a result of severe airflow obstruction. Bronchial casts may be associated with congenital and acquired cardiopathies, bronchopulmonary diseases leading to mucus hypersecretion, and pulmonary lymphatic abnormalities. In recent years, however, there is growing evidence that plastic bronchitis can also be triggered by common respiratory tract infections and thereby cause atelectasis even in otherwise healthy children. CASE PRESENTATION: We report on 22-month-old monozygotic twins presenting with atelectasis triggered by a simple respiratory tract infection. The clinical, laboratory, and radiographic findings given, bronchial cast formation was suspected in both infants but could only be confirmed after bronchoscopy in the first case. Real-time polymerase chain reaction of the removed cast as well as nasal lavage fluid of both infants demonstrated strong positivity for human bocavirus. CONCLUSION: Our case report is the first to describe two simultaneously affected monozygotic twins and substantiates the hypothesis of a contributing genetic factor in the pathophysiology of this disease. In this second report related to human bocavirus, we show additional evidence that this condition can be triggered by a simple respiratory tract infection in previously healthy infants.

Optimising success of neonatal extubation: Respiratory support.

In this review, we examine lung physiology before, during and after neonatal extubation and propose a three-phase model for the extubation procedure. We perform meta-analyses to compare different modes of non-invasive respiratory support after neonatal extubation and based on the findings, the following clinical recommendations are made.

Early prediction of pulmonary outcomes in preterm infants using electrical impedance tomography.

Introduction: Electrical impedance tomography (EIT) allows assessment of ventilation and aeration homogeneity which may be associated with respiratory outcomes in preterm infants. Methods: This was a secondary analysis to a recent randomized controlled trial in very preterm infants in the delivery room (DR). The predictive value of various EIT parameters assessed 30 min after birth on important respiratory outcomes (early intubation <24 h after birth, oxygen dependency at 28 days after birth, and moderate/severe bronchopulmonary dysplasia; BPD) was assessed. Results: Thirty-two infants were analyzed. A lower percentage of aerated lung volume [OR (95% CI) = 0.8 (0.66-0.98), p = 0.027] as well as a higher aeration homogeneity ratio (i.e., more aeration in the non-gravity-dependent lung) predicted the need for supplemental oxygen at 28 days after birth [9.58 (5.16-17.78), p = 0.0028]. Both variables together had a similar predictive value to a model using known clinical contributors. There was no association with intubation or BPD, where numbers were small. Discussion: In very preterm infants, EIT markers of aeration at 30 min after birth accurately predicted the need for supplemental oxygen at 28 days after birth but not BPD. EIT-guided individualized optimization of respiratory support in the DR may be possible.

Case report: Intrapulmonary tidal volumes in a preterm infant with chest wall rigidity.

Background: Chest wall rigidity is a known side effect of fentanyl use, which is why fentanyl is usually combined with a muscle relaxant such as mivacurium. Verifying endotracheal intubation is difficult in case of a rigid chest wall. Case presentation: We present the case of a preterm infant (29 completed weeks gestation, birth weight 1,150 g) with a prolonged chest wall rigidity after fentanyl administration for intubation despite adequate doses of mivacurium. This resulted in a pronounced desaturation without any effect on heart rate. Clinically, the infant showed no chest wall movement despite intubation and common tools to verify intubation (including end-tidal carbon dioxide measurement and auscultation) were inconclusive. However, using electrical impedance tomography (EIT), we were able to demonstrate minimal tidal volumes at lung level and thereby, EIT was able to accurately show correct placement of the endotracheal tube. Conclusions: This case may increase vigilance for fentanyl-induced chest wall rigidity in the neonatal population even when simultaneously administering mivacurium. Higher airway pressures exceeding 30 mmHg and the use of µ-receptor antagonists such as naloxone should be considered to reverse opioid-induced chest wall rigidity. Most importantly, our data may imply a relevant clinical benefit of using EIT during neonatal intubation as it may accurately show correct endotracheal tube placement.

Intrapulmonary Volume Changes during Hiccups versus Spontaneous Breaths in a Preterm Infant.

Hiccups occur at all ages but are most common during fetal development, and accordingly, they are seen regularly in preterm infants. However, the physiologic correlate of hiccups has never been established. We present the case of a preterm infant who developed a spell of hiccups and compared lung volume changes during hiccups with spontaneous breaths using electrical impedance tomography. Hiccups mostly occurred during the expiratory phase of breathing and were associated with a shorter inspiratory time and a larger tidal volume compared with spontaneous breaths. The center of ventilation was shifted toward the ventral (non-gravity-dependent) part of the lung during hiccups and volume changes were mainly restricted to the larger airways, but some gas flow also reached the lung parenchyma. Our observations shed new light on this phenomenon, which is well known but little researched, and our findings may imply a physiological impact of hiccups during fetal development.

Effect of Early High-Dose Recombinant Human Erythropoietin on Behavior and Quality of Life in Children Aged 5 Years Born Very Preterm: Secondary Analysis of a Randomized Clinical Trial.

Importance: In light of the promising neuroprotective properties of recombinant human erythropoietin (RHEpo), the Swiss EPO Neuroprotection Trial was started to investigate its effect on neurodevelopment in very preterm infants. The results of the primary and secondary outcome analysis did not show any effect of RHEpo on cognitive performance, neuromotor outcomes, or somatic growth of the study participants at ages 2 or 5 years. Objective: To investigate whether early high-dose RHEpo improves behavioral outcomes and health-related quality of life (HRQoL) at age 5 years. Design, Setting, and Participants: This was a prespecified secondary analysis of the double-blind, placebo-controlled, multicenter Swiss EPO Neuroprotection randomized clinical trial, which was conducted at 5 level-III perinatal centers in Switzerland. Infants born between 26 weeks 0 days' and 31 weeks 6 days' gestation were recruited between 2005 and 2012 and followed-up until age 5 years (last follow-up in 2018). Data were analyzed from January 6 to December 31, 2021. Interventions: Infants were assigned to receive either RHEpo (3000 IU/kg) or placebo (saline, 0.9%) intravenously 3 times within the first 42 hours after birth. Main Outcomes and Measures: The prespecified parent-reported measures of behavioral outcomes and health-related quality of life (HRQoL) of their children at the age of 5 years were assessed by two standardized questionnaires: the Strengths and Difficulties Questionnaire (behavioral outcomes) and the KIDSCREEN-27 (HRQoL). Results: Among 448 randomized infants, 228 infants were assigned to the RHEpo group and 220 infants were assigned to the placebo group. Questionnaire data were available for 317 children (71%) at a mean (SD) age of 5.8 (0.4) years (mean [SD] gestational age at birth, 29.3 [1.6] weeks; mean [SD] birth weight 1220 [340] grams; 128 [40%] female infants). At the age 5 years follow-up, the mean (SD) total difficulties score in the RHEpo group (8.41 [5.60] points) was similar to that of the placebo group (7.76 [4.81]) (P = .37). There were no statistically significant differences between the groups in any other outcome measures. Conclusions and Relevance: This secondary analysis of a randomized clinical trial showed no evidence for an effect of early high-dose RHEpo administration on behavioral outcomes or HRQoL in children born very preterm at early school age. Trial Registration: ClinicalTrials.gov Identifier: NCT00413946.