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.

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).

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.

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.

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.

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.

"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.

Safety and Short-term Outcomes of High-Dose Erythropoietin in Preterm Infants With Intraventricular Hemorrhage: The EpoRepair Randomized Clinical Trial.

Importance: Intraventricular hemorrhage (IVH) is a major cause of neonatal morbidity and mortality in preterm infants without a specific medical treatment to date. Objective: To assess the safety and short-term outcomes of high-dose erythropoietin in preterm infants with IVH. Design, Setting, and Participants: Between April 1, 2014, and August 3, 2018, a randomized double-blind clinical trial enrolled 121 preterm infants (gestational age <32 weeks or birth weight <1500 g) aged 8 or less days with moderate to severe IVH identified by cerebral ultrasonography from 8 Swiss and Austrian tertiary neonatal units. Statistical analyses were performed between October 1, 2019, and September 12, 2022. Interventions: Infants received intravenous high-dose erythropoietin (2000 units/kg body weight) or placebo at 4 time points between weeks 1 and 4 of life. Main Outcomes and Measures: Secondary outcomes included (1) mortality and morbidity rates and (2) brain magnetic resonance imaging findings at term-equivalent age (TEA). The primary outcome was the composite intelligence quotient at 5 years of age (not available before 2023). Results: Sixty infants (48% male [n = 29]) were randomly assigned to receive erythropoietin, and 61 infants (61% male [n = 37]) were randomly assigned to receive placebo. The median birth weight was 832 g (IQR, 687-990 g) in the erythropoietin group and 870 g (IQR, 680-1110 g) in the placebo group. Median gestation was 26.1 weeks (IQR, 24.8-27.3 weeks) in the erythropoietin group and 27.0 weeks (24.9-28.1 weeks) in the placebo group. The 2 groups had similar baseline characteristics and morbidities. Up to TEA, 10 newborns died (16.7%) in the erythropoietin group, and 5 newborns (8.2%) died in the placebo group (adjusted odds ratio, 2.24 [95% CI, 0.74-7.66]; P = .15). Infants receiving erythropoietin had higher mean hematocrit levels. Conventional magnetic resonance imaging at TEA for 100 infants showed no significant differences in global or regional brain injury scores. Conclusions and Relevance: This preliminary report of a randomized clinical trial found no evidence that high-dose erythropoietin in preterm infants with IVH affects brain injury scores on conventional magnetic resonance imaging at TEA. Higher mortality in the erythropoietin group was not significant but should be reassessed based on future results from similar trials. Trial Registration: ClinicalTrials.gov Identifier: NCT02076373.

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.

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).

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.

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.

Nasal Intermittent Positive Pressure Ventilation for Neonatal Respiratory Distress Syndrome.

Nasal or noninvaisve intermittent positive pressure ventilation (NIPPV) refers to well-established noninvasive respiratory support strategies combining a continuous distending pressure with intermittent pressure increases. Uncertainty remains regarding the benefits provided by the various devices and techniques used to generate NIPPV. Our included meta-analyses of trials comparing NIPPV with continuous positive airway pressure (CPAP) in preterm infants demonstrate that both primary and postextubation NIPPV are superior to CPAP to prevent respiratory failure leading to additional ventilatory support. This short-term benefit is associated with a reduction in bronchopulmonary dysplasia, but not with mortality. Benefits are greatest when ventilator-generated, synchronized NIPPV is used.

Surfactant Nebulization to Prevent Intubation in Preterm Infants: A Systematic Review and Meta-analysis.

CONTEXT: Surfactant nebulization (SN) may offer a safe alternative for surfactant administration in respiratory distress syndrome of preterm infants. OBJECTIVE: To evaluate the efficacy of SN for the prevention of early intubation. DATA SOURCES: Medline, Embase, The Cochrane Library, clinicaltrials.gov, published abstracts, and references of relevant articles were searched through March 23, 2021. STUDY SELECTION: Randomized clinical trials of preterm infants <37 weeks' gestation comparing SN with noninvasive respiratory support or intratracheal surfactant application. DATA EXTRACTION: Two reviewers extracted data and assessed risk of bias from included studies separately and blinded. Data were pooled by using a fixed-effects model. Subgroups (gestational age, type of nebulizer, surfactant type, and dosage) were evaluated. Primary outcome was intubation rate at 72 hours after birth. RESULTS: Nine studies recruiting 1095 infants met inclusion criteria. SN compared with standard care significantly reduced intubation rate at 72 hours after birth (226 of 565 infants [40.0%] vs 231 of 434 infants [53.2%]; risk ratio [RR]: 0.73, 95% confidence interval [CI]: 0.63-0.84; number needed to treat: 8; 95% CI: 5-14]). Prespecified subgroup analysis identified important heterogeneity: SN was most effective in infants ≥28 weeks' gestation (RR: 0.70, 95% CI: 0.60-0.82), with a pneumatically driven nebulizer (RR: 0.52, 95% CI: 0.40-0.68) and in infants receiving ≥200 mg/kg and animal-derived surfactant (RR: 0.63, 95% CI: 0.52-0.75). No differences in neonatal morbidities or mortality were identified. LIMITATIONS: Quality of evidence was low owing to risk of bias and imprecision. CONCLUSIONS: SN reduced the intubation rate in preterm infants with a higher efficacy for specific subgroups. There was no difference in relevant neonatal morbidities or mortality.

Genetic Analysis in a Swiss Cohort of Bilateral Congenital Cataract.

IMPORTANCE: Identification of geographic population-based differences in genotype and phenotype heterogeneity are important for targeted and patient-specific diagnosis and treatment, counseling, and screening strategies. OBJECTIVE: To report disease-causing variants and their detailed phenotype in patients with bilateral congenital cataract from a single center in Switzerland and thereby draw a genetic map and perform a genotype-phenotype comparison of this cohort. DESIGN, SETTING, AND PARTICIPANTS: This clinical and molecular-genetic cohort study took place through the collaboration of the Department of Ophthalmology at the University Hospital Zurich and the Institute of Medical Molecular Genetics, University of Zurich, Schlieren, Switzerland. Thirty-seven patients from 25 families with different types of bilateral congenital cataract were included. All participating family members received a comprehensive eye examination. Whole exome sequencing was performed in the index patients, followed by a filtering process to detect possible disease-associated variants in genes previously described in association with congenital cataract. Probable disease-causing variants were confirmed by Sanger sequencing in available family members. All data were collected from January 2018 to June 2020, and the molecular-genetic analyses were performed from January 2019 to July 2020. MAIN OUTCOMES AND MEASURES: Identification of the underlying genetic causes of bilateral congenital cataract, including novel disease-causing variants and phenotype correlation. RESULTS: Among the 37 patients (18 [49%] male and 19 [51%] female; mean [SD] age, 17.3 [15.9] years) from 25 families, pathogenic variants were detected in 20 families (80% detection rate), which included 13 novel variants in the following genes: BCOR, COL4A1, CRYBA2, CRYBB2, CRYGC, CRYGS, GJA3, MAF, NHS, and WFS1. Putative disease-causing variants were identified in 14 of 20 families (70%) as isolated cases and in 6 of 20 families (30%) with syndromic cases. A recessive variant in the CRYBB2 gene in a consanguineous family with 2 affected siblings showing a nuclear and sutural cataract was reported in contrast to previously published reports. In addition, the effect on splicing in a minigene assay of a novel splice site variant in the NHS gene (c.[719-2A>G]) supported the pathogenicity of this variant. CONCLUSIONS AND RELEVANCE: This study emphasizes the importance of genetic testing of congenital cataracts. Known dominant genes need to be considered for recessive inheritance patterns. Syndromic types of cataract may be underdiagnosed in patients with mild systemic features.

Does surfactant nebulization prevent early intubation in preterm infants? A protocol for a systematic review and meta-analysis.

BACKGROUND: Respiratory distress syndrome (RDS) is the most common cause of respiratory failure in preterm infants. Treatment consists of respiratory support and exogenous surfactant administration. Commonly, surfactant is administered intratracheally. However, this requires airway instrumentation and subsequent fluid instillation which may be harmful. Surfactant nebulization (SN) may offer a safe and effective alternative for surfactant administration, but the clinical efficacy is not yet established. Thus, this systematic review and meta-analysis of randomized controlled trials will summarize the available evidence to determine the effectiveness and safety of SN for the prevention of intubation and subsequent mechanical ventilation at 72 h after birth. METHODS: A systematic literature search in Medline, Embase, and The Cochrane Library will be performed, and all randomized controlled trials (RCTs) and quasi-RCTs from published articles, presentations, and trial registries will be included in this meta-analysis. Titles and abstracts of all records identified in the search will be screened by two reviewers independently. Data on preterm infants (≤ 37 weeks) receiving nebulized surfactant in the first 72 h after birth for the treatment or prevention of RDS will be evaluated. Primary outcome is the intubation rate by 72 h after birth, and secondary outcomes include peridosing safety effects as well as major neonatal morbidities. Risk of bias will be assessed using the revised Cochrane ROB tool, and subgroup analyses will be performed to evaluate potential confounding factors. Publication bias will be assessed by examining a funnel plot. The meta-analysis will be performed using a fixed-effects model. DISCUSSION: This review will provide an evidence-based tool for information about surfactant nebulization, illustrating the current knowledge and hopefully revealing potential novel avenues for researchers and clinicians alike. SYSTEMATIC REVIEW REGISTRATION: This review is registered with the publicly available resource PROSPERO ( CRD42020175625 ).

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.