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.

Excellent outcome of stem cell transplantation for sickle cell disease.

Many sickle cell disease (SCD) patients lack matched family donors (MFD) or matched unrelated donors (MUD), implying haploidentical donors (MMFD) as a logical donor choice. We used a reduced toxicity protocol for all donor types. We included 31 patients (2-22 years) with MFD (n = 15), MMFD (10), or MUD (6) HSCT and conditioning with alemtuzumab/ATG, thiotepa, fludarabine and treosulfan, and post-transplant cyclophosphamide for MMFD. After the initial six patients, treosulfan was replaced by targeted busulfan (AUC 65-75 ng*h/ml). After a median follow-up of 26 months (6-123), all patients are alive and off immunosuppression. Two MMFD patients experienced secondary graft failure with recurrence of SCD, both after treosulfan conditioning. Neither acute GVHD ≥ °III nor moderate/severe chronic GVHD was observed. The disease-free, severe GVHD-free survival was 100%, 100%, and 80% in the MFD, MUD, and MMFD groups, respectively (p = 0.106). There was a higher rate of virus reactivation in MMFD (100%) and MUD (83%) compared to MFD (40%; p = 0.005), but not of viral disease (20% vs 33% vs 13%; p = 0.576). Six patients had treosulfan-based conditioning, two of whom experienced graft failure (33%), compared to 0/25 (0%) after busulfan-based conditioning (p = 0.032). Donor chimerism was ≥ 80% in 28/31 patients (90%) at last follow-up. Reduced toxicity myeloablative conditioning resulted in excellent overall survival, negligible GVHD, and low toxicity among all donor groups in pediatric and young adult patients with SCD.

Maternal knowledge of recommendations for safe infant sleep and intentions for implementation - a cross sectional analysis of data from the KUNO-Kids birth cohort study.

OBJECTIVES: Despite major advances in prevention, sudden infant death syndrome (SIDS) remains an important cause of infant mortality. The aim of our study was to determine actual knowledge and intentions to implement SIDS prevention measures among new mothers and to identify potential knowledge gaps for improved postpartum counselling strategies. METHODS: Data was collected in a standardized interview from participants of the KUNO-Kids birth cohort study before discharge from maternity ward. The mothers did not receive any specific teaching prior to the interview. RESULTS: The majority of 2,526 interviewed mothers were able to actively report important recommendations for safe infant sleep, including the exclusive face-up position. However, 154 mothers (9%) intended to position the newborn face-down sometimes or often. The most frequently envisaged sleeping furniture was a bedside sleeper (n=1,144, 47%), but 2.2% of mothers indicated that the intended default sleeping place for the newborn would be the parents' bed (which is discouraged by the recommendations). For 43% of the infants (n=1,079), mothers planned to have loose objects in the bed and 189 mothers (7%) intended to use a loose blanket. 22% of infants (n=554) will live in a household with a smoker. Multivariate regression showed a significant association of "good knowledge" with maternal age and with not being a single parent, whereas the household size was negatively associated. CONCLUSION: Although the majority of mothers in our birth cohort were aware of many recommendations for safe infant sleep, our data also uncovered weaknesses in SIDS prevention knowledge and point to specific areas with potential for improved counselling.

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.

Food allergy in infants assessed in two German birth cohorts 10 years after the EuroPrevall Study.

BACKGROUND: The prevalence of food allergies (FA) in children increased rapidly at the turn of the century. The EuroPrevall study identified Germany as a country with very high prevalence of FA at that time. Using two large German birth cohorts, we provide an update of the status quo 10 years later. METHODS: KUNO Kids and Ulm SPATZ Health studies are two ongoing prospective birth cohorts. Information on FA was obtained by questionnaires at birth and after 6, 12, and 24 months. Univariable and multivariable logistic regression analyses were performed to investigate risk factors during pregnancy, birth, and early childhood. RESULTS: In 1139 and 1006 children from KUNO Kids and SPATZ, the point prevalence of parent-reported FA symptoms at the ages of 1 and 2 years was 13.2% (95% CI: 11.2-15.2) and 13.9% (95% CI: 11.5-17.2) in KUNO Kids. Doctor's diagnosed FA at 1 and 2 years was 2.4% (95% CI: 1.6-3.4) and 2.7% (95% CI: 1.2-4.3) in KUNO Kids and 2.3% (95% CI: 1.3-3.6) and 3% (95% CI: 2.0-4.5) in SPATZ. Cow's milk and citrus fruits were most frequently suspected by parents to cause FA symptoms. Atopy in the child was associated with a higher frequency of FA at any time, whereas atopy in first-degree relatives was only associated with FA at year 1. Smoke exposure during pregnancy was a risk for FA at age 2. CONCLUSION: The prevalence of food allergy seems to have plateaued in the last 10 years in Germany. FA is often suspected by parents but only rarely diagnosed by oral food challenge. Risk factor analysis may help to establish personalized health approaches.

"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).

6q12 and 11p14 variants are associated with postnatal exhaled nitric oxide levels and respiratory symptoms.

BACKGROUND: Exhaled nitric oxide (eNO) is a biomarker of airway inflammation and seems to precede respiratory symptoms, such as asthma, in childhood. Identifying genetic determinants of postnatal eNO levels might aid in unraveling the role of eNO in epithelial function or airway inflammation and disease. OBJECTIVE: We sought to identify genetic determinants of early postnatal eNO levels and subsequent respiratory symptoms during the first year of life. METHODS: Within a population-based birth cohort, eNO levels were measured in healthy term infants aged 5 weeks during quiet tidal breathing in unsedated sleep. We assessed associations of single nucleotide polymorphisms with eNO levels in a genome-wide association study and subsequent symptoms of lower respiratory tract infections during the first year of life and asked whether this was modified by prenatal and early-life environmental factors. RESULTS: We identified thus far unknown determinants of infant eNO levels: rs208515 (P = 3.3 × 10-8), which is located at 6q12, probably acting in "trans" and explaining 10.3% of eNO level variance, and rs1441519 (P = 1.6 × 10-6), which is located at 11p14, potentially affecting nitric oxide synthase 3 (NOS3) expression, as shown by means of in vitro functional analyses. Moreover, the 6q12 locus was inversely associated with subsequent respiratory symptoms (P < .05) and time to recovery after first respiratory symptoms during the first year of life (P < .05). CONCLUSION: The identification of novel genetic determinants of infant eNO levels might implicate that postnatal eNO metabolism in healthy infants before first viral infections and sensitization is related to mechanisms other than those associated with asthma, atopy, or increased risk thereof later in life.

Doublesex and mab-3 related transcription factor 1 (DMRT1) is a sex-specific genetic determinant of childhood-onset asthma and is expressed in testis and macrophages.

BACKGROUND: Asthma is a disease affecting more boys than girls in childhood and more women than men in adulthood. The mechanisms behind these sex-specific differences are not yet understood. OBJECTIVE: We analyzed whether and how genetic factors contribute to sex-specific predisposition to childhood-onset asthma. METHODS: Interactions between sex and polymorphisms on childhood asthma risk were evaluated in the Multicentre Asthma Genetics in Childhood Study (MAGICS)/Phase II International Study of Asthma and Allergies in Childhood (ISAAC II) population on a genome-wide level, and findings were validated in independent populations. Genetic fine mapping of sex-specific asthma association signals was performed, and putatively causal polymorphisms were characterized in vitro by using electrophoretic mobility shift and luciferase activity assays. Gene and protein expression of the identified gene doublesex and mab-3 related transcription factor 1 (DMRT1) were measured in different human tissues by using quantitative real-time PCR and immunohistochemistry. RESULTS: Polymorphisms in the testis-associated gene DMRT1 displayed interactions with sex on asthma status in a population of primarily clinically defined asthmatic children and nonasthmatic control subjects (lowest P = 5.21 × 10(-6)). Replication of this interaction was successful in 2 childhood populations clinically assessed for asthma but showed heterogeneous results in other population-based samples. Polymorphism rs3812523 located in the putative DMRT1 promoter was associated with allele-specific changes in transcription factor binding and promoter activity in vitro. DMRT1 expression was observed not only in the testis but also in lung macrophages. CONCLUSION: DMRT1 might influence sex-specific patterns of childhood asthma, and its expression in testis tissue and lung macrophages suggests a potential involvement in hormone or immune cell regulation.

Polymorphisms related to ORMDL3 are associated with asthma susceptibility, alterations in transcriptional regulation of ORMDL3, and changes in TH2 cytokine levels.

BACKGROUND: Chromosome 17q21, harboring the orosomucoid 1-like 3 (ORMDL3) gene, has been consistently associated with childhood asthma in genome-wide association studies. OBJECTIVE: We investigated genetic variants in and around ORMDL3 that can change the function of ORMDL3 and thus contribute to asthma susceptibility. METHODS: We performed haplotype analyses and fine mapping of the ORMDL3 locus in a cross-sectional (International Study of Asthma and Allergies in Childhood Phase II, n = 3557 total subjects, n = 281 asthmatic patients) and case-control (Multicenter Asthma Genetics in Childhood Study/International Study of Asthma and Allergies in Childhood Phase II, n = 1446 total subjects, n = 763 asthmatic patients) data set to identify putative causal single nucleotide polymorphisms (SNPs) in the locus. Top asthma-associated polymorphisms were analyzed for allele-specific effects on transcription factor binding and promoter activity in vitro and gene expression in PBMCs after stimulation ex vivo. RESULTS: Two haplotypes (H1 and H2) were significantly associated with asthma in the cross-sectional (P = 9.9 × 10(-5) and P = .0035, respectively) and case-control (P = 3.15 × 10(-8) and P = .0021, respectively) populations. Polymorphisms rs8076131 and rs4065275 were identified to drive these effects. For rs4065275, a quantitative difference in transcription factor binding was found, whereas for rs8076131, changes in upstream stimulatory factor 1 and 2 transcription factor binding were observed in vitro by using different cell lines and PBMCs. This might contribute to detected alterations in luciferase activity paralleled with changes in ORMDL3 gene expression and IL-4 and IL-13 cytokine levels ex vivo in response to innate and adaptive stimuli in an allele-specific manner. Both SNPs were in strong linkage disequilibrium with asthma-associated 17q21 SNPs previously related to altered ORMDL3 gene expression. CONCLUSION: Polymorphisms in a putative promoter region of ORMDL3, which are associated with childhood asthma, alter transcriptional regulation of ORMDL3, correlate with changes in TH2 cytokines levels, and therefore might contribute to the childhood asthma susceptibility signal from 17q21.

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.

Defining familial longevity and developing a familial longevity score for unbiased epigenetic studies in a birth cohort.

Aim: Longevity accumulating in families has genetic and epigenetic components. To study early and unbiased epigenetic predictors of longevity prospectively, a birth cohort would be ideal. However, the original family longevity selection score (FLoSS) focuses on populations of elderly only.Methods: In the German birth cohort KUNO-Kids we assessed when information for such scores may be best collected and how to calculate an adapted FLoSS.Results: A total of 551 families contributed to adapted FLoSS, with a mean score of -0.15 (SD 2.33). Adapted FLoSS ≥7 as a marker of exceptional longevity occurred in 3.3% of families, comparable to original FLoSS in elderly.Conclusion: An adapted FLoSS from data collectable postnatally may be a feasible tool to study unbiased epigenetic predictors for longevity.

In the German birth cohort KUNO-Kids we assessed if and how a family longevity selection score may best be calculated to study unbiased epigenetic predictors for longevity in the future.

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.

Prophylactic surfactant nebulisation for the early aeration of the preterm lung: a randomised clinical trial.

OBJECTIVE: The effect of prophylactic surfactant nebulisation (SN) is unclear. We aimed to determine whether prophylactic SN improves early lung aeration. DESIGN: Parallel, randomised clinical trial, conducted between March 2021 and January 2022. SETTING: Delivery room (DR) of a tertiary neonatal centre in Zurich, Switzerland. PATIENTS: Preterm infants between 26 0/7 and 31 6/7 weeks gestation INTERVENTIONS: Infants were randomised to receive positive distending pressure alone or positive distending pressure and additional SN (200 mg/kg; poractant alfa) using a customised vibrating membrane nebuliser. SN commenced with the first application of a face mask immediately after birth. MAIN OUTCOME MEASURES: Primary outcome was the difference in end-expiratory lung impedance from birth to 30 min after birth (∆EELI30min). EELI correlates well with functional residual capacity. Secondary outcomes included physiological and clinical outcomes. RESULTS: Data from 35 infants were collected, and primary outcome data were analysed from 32 infants (n=16/group). Primary outcome was not different between intervention and control group (median (IQR): 25 (7-62) vs 10 (0-26) AU/kg, p=0.21). ∆EELI was slightly higher in the intervention group at 6 and 12 hours after birth, particularly in the central areas of the lung. There were no differences in cardiorespiratory and clinical parameters. Two adverse events were noted in the intervention group. CONCLUSIONS: Prophylactic SN in the DR did not significantly affect ∆EELI30min and showed only minimal effects on lung physiology. Prophylactic SN in the DR was feasible. There were no differences in clinical outcomes. TRIAL REGISTRATION NUMBER: NCT04315636.

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.

Implementation of safe infant sleep recommendations during night-time sleep in the first year of life in a German birth cohort.

The aim of our study was to assess the extent to which families followed recommendations, issued by the German society for sleep medicine, for the prevention of sudden infant death syndrome (SIDS) during night-time sleep. Analyzing longitudinal data from a birth cohort located at the University Children's Hospital Regensburg in Bavaria (Germany), we determined data regarding the infant's sleep location, sleep settings and body position, and exposure to environmental factors. Data were collected in a structured interview after birth and by standardized questionnaires at 4 weeks, 6 months, and 1 year of life, respectively. The majority of 1,400 surveyed infants (94% at 4 weeks) were reported to sleep in the parents' sleeping room during the first months of life. While the most common furniture was a bedside sleeper (used by 48%), we also observed a considerable proportion of families who regularly practiced bed-sharing and, for 16% of infants, the parents' bed was the default sleeping place. 12% of infants were still put regularly in the prone position. The vast majority (87%) of the infants were breastfed at some timepoint and 17% lived in a household with one or more smokers. Although most parents implemented many SIDS recommendations, our analysis illustrates a considerable gap between recommendations and intentions after birth on the one hand and actual implementation in real life on the other. The number-one deviation from the current SIDS guidelines during night-time sleep was bed-sharing with an adult.

Lung volume changes during apnoeas in preterm infants.

OBJECTIVE: Mechanisms of non-invasive high-frequency oscillatory ventilation (nHFOV) in preterm infants are unclear. We aimed to compare lung volume changes during apnoeas in preterm infants on nHFOV and nasal continuous positive airway pressure (nCPAP). METHODS: Analysis of electrical impedance tomography (EIT) data from a randomised crossover trial comparing nHFOV with nCPAP in preterm infants at 26-34 weeks postmenstrual age. EIT data were screened by two reviewers to identify apnoeas ≥10 s. End-expiratory lung impedance (EELI) and tidal volumes (VT) were calculated before and after apnoeas. Oxygen saturation (SpO2) and heart rate (HR) were extracted for 60 s after apnoeas. RESULTS: In 30 preterm infants, 213 apnoeas were identified. During apnoeas, oscillatory volumes were detectable during nHFOV. EELI decreased significantly during apnoeas (∆EELI nCPAP: -8.0 (-11.9 to -4.1) AU/kg, p<0.001; ∆EELI nHFOV: -3.4 (-6.5 to -0.3), p=0.03) but recovered over the first five breaths after apnoeas. Compared with before apnoeas, VT was increased for the first breath after apnoeas during nCPAP (∆VT: 7.5 (3.1 to 11.2) AU/kg, p=0.001). Falls in SpO2 and HR after apnoeas were greater during nCPAP than nHFOV (mean difference (95% CI): SpO2: 3.6% (2.7 to 4.6), p<0.001; HR: 15.9 bpm (13.4 to 18.5), p<0.001). CONCLUSION: Apnoeas were characterised by a significant decrease in EELI which was regained over the first breaths after apnoeas, partly mediated by a larger VT. Apnoeas were followed by a considerable drop in SpO2 and HR, particularly during nCPAP, leading to longer episodes of hypoxemia during nCPAP. Transmitted oscillations during nHFOV may explain these benefits. TRIAL REGISTRATION NUMBER: ACTRN12616001516471.

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.