At the threshold of viability: to resuscitate or not to resuscitate - the perspectives of Israeli neonatologists.

OBJECTIVE: This study aims to examine the perspectives of neonatologists in Israel regarding resuscitation of preterm infants born at 22-24 weeks gestation and their consideration of parental preferences. The factors that influence physicians' decisions on the verge of viability were investigated, and the extent to which their decisions align with the national clinical guidelines were determined. STUDY DESIGN: Descriptive and correlative study using a 47-questions online questionnaire. RESULTS: 90 (71%) of 127 active neonatologists in Israel responded. 74%, 50% and 16% of the respondents believed that resuscitation and full treatment at birth are against the best interests of infants born at 22, 23 and 24 weeks gestation, respectively. Respondents' decisions regarding resuscitation of extremely preterm infants showed significant variation and were consistently in disagreement with either the national clinical guidelines or the perception of what is in the best interest of these newborns. Gender, experience, country of birth and the level of religiosity were all associated with respondents' preferences regarding treatment decisions. Personal values and concerns about legal issues were also believed to affect decision-making. CONCLUSION: Significant variation was observed among Israeli neonatologists regarding delivery room management of extremely premature infants born at 22-24 weeks gestation, usually with a notable emphasis on respecting parents' wishes. The current national guidelines do not fully encompass the wide range of approaches. The country's guidelines should reflect the existing range of opinions, possibly through a broad survey of caregivers before setting the guidelines and recommendations.

National Rapid Genome Sequencing in Neonatal Intensive Care.

Importance: National implementation of rapid trio genome sequencing (rtGS) in a clinical acute setting is essential to ensure advanced and equitable care for ill neonates. Objective: To evaluate the feasibility, diagnostic efficacy, and clinical utility of rtGS in neonatal intensive care units (NICUs) throughout Israel. Design, Setting, and Participants: This prospective, public health care-based, multicenter cohort study was conducted from October 2021 to December 2022 with the Community Genetics Department of the Israeli Ministry of Health and all Israeli medical genetics institutes (n = 18) and NICUs (n = 25). Critically ill neonates suspected of having a genetic etiology were offered rtGS. All sequencing, analysis, and interpretation of data were performed in a central genomics center at Tel-Aviv Sourasky Medical Center. Rapid results were expected within 10 days. A secondary analysis report, issued within 60 days, focused mainly on cases with negative rapid results and actionable secondary findings. Pathogenic, likely pathogenic, and highly suspected variants of unknown significance (VUS) were reported. Main Outcomes and Measures: Diagnostic rate, including highly suspected disease-causing VUS, and turnaround time for rapid results. Clinical utility was assessed via questionnaires circulated to treating neonatologists. Results: A total of 130 neonates across Israel (70 [54%] male; 60 [46%] female) met inclusion criteria and were recruited. Mean (SD) age at enrollment was 12 (13) days. Mean (SD) turnaround time for rapid report was 7 (3) days. Diagnostic efficacy was 50% (65 of 130) for disease-causing variants, 11% (14 of 130) for VUS suspected to be causative, and 1 novel gene candidate (1%). Disease-causing variants included 12 chromosomal and 52 monogenic disorders as well as 1 neonate with uniparental disomy. Overall, the response rate for clinical utility questionnaires was 82% (107 of 130). Among respondents, genomic testing led to a change in medical management for 24 neonates (22%). Results led to immediate precision medicine for 6 of 65 diagnosed infants (9%), an additional 2 (3%) received palliative care, and 2 (3%) were transferred to nursing homes. Conclusions and Relevance: In this national cohort study, rtGS in critically ill neonates was feasible and diagnostically beneficial in a public health care setting. This study is a prerequisite for implementation of rtGS for ill neonates into routine care and may aid in design of similar studies in other public health care systems.

Transcutaneous CO2 Monitoring in Extremely Low Birth Weight Premature Infants.

Extremely low birth weight (ELBW) premature infants are particularly susceptible to hypocarbia and hypercarbia, which are associated with brain and lung morbidities. Transcutaneous CO2 (TcCO2) monitoring allows for continuous non-invasive CO2 monitoring during invasive and non-invasive ventilation and is becoming more popular in the NICU. We aimed to evaluate the correlation and agreement between CO2 levels measured by a TcCO2 monitor and blood gas CO2 (bgCO2) among ELBW infants. This was a prospective observational multicenter study. All infants < 1000 g admitted to the participating NICUs during the study period were monitored by a TcCO2 monitor, if available. For each bgCO2 measured, a simultaneous TcCO2 measurement was documented. In total, 1828 pairs of TcCO2-bgCO2 values of 94 infants were collected, with a median (IQR) gestational age of 26.4 (26.0, 28.3) weeks and birth weight of 800 (702, 900) g. A moderate correlation (Pearson: r = 0.64) and good agreement (bias (95% limits of agreement)):(2.9 [-11.8, 17.6] mmHg) were found between the TcCO2 and bgCO2 values in the 25-70 mmHg TcCO2 range. The correlation between the TcCO2 and bgCO2 trends was moderate. CO2 measurements by TcCO2 are in good agreement (bias < 5 mmHg) with bgCO2 among premature infants < 1000 g during the first week of life, regardless of day of life, ventilation mode (invasive/non-invasive), and sampling method (arterial/capillary/venous). However, wide limits of agreement and moderate correlation dictate the use of TcCO2 as a complementary tool to blood gas sampling, to assess CO2 levels and trends in individual patients.

Is there room for prompt routine ophthalmic examination in neonates with congenital cytomegalovirus (CMV) infection during the neonatal period?

PURPOSE: To establish the clinical necessity of routine targeted ophthalmic examination of newborns with congenital cytomegalovirus (CMV) infection during the neonatal period. METHODS: This retrospective study included consecutive neonates that were referred for ophthalmological screening within the context of a proven congenital CMV infection. The presence of CMV-related ocular and systemic findings was determined. RESULTS: Among the 91 patients included in this study, 72 (79.12%) were symptomatic with one or more of the following manifestations: abnormal brain ultrasound (42; 46.15%), small for gestational age (29; 31.87%), microcephaly (23; 25.27%), thrombocytopenia (14; 15.38%), sensory neural hearing loss (13; 14.29%), neutropenia (12; 13.19%), anemia (4; 4.4%), skin lesions (4; 4.4%), hepatomegaly (3; 3.3%), splenomegaly (3; 3.3%), direct hyperbilirubinemia (2; 2.2%). Not one single neonate in this cohort had any of the ocular findings surveyed. CONCLUSION: The presence of ophthalmological findings among neonates with congenital CMV infection during the neonatal period is infrequent, suggesting that routine ophthalmological screening may be safely deferred for the post-neonatal period.

Oxygenation Instability during Bolus versus Continuous Feeding among Very Low Birth Weight Premature Infants, Supported by Noninvasive Ventilation: A Randomized Prospective Study.

OBJECTIVE: This study aimed to compare oxygenation instability, as documented by the oxygen saturation (SpO2) histograms, during bolus (over 30 minutes) versus continuous (over 2 hours) feeding among very low birth weight (VLBW) premature infants, supported with noninvasive ventilation (NIV). STUDY DESIGN: This was a randomized prospective study. VLBW infants supported with NIV received three consecutive feeds in a random order of bolus-continuous-bolus or continuous-bolus-continuous. During each feed, 30 minutes and 2 hours histograms were documented. RESULTS: Twenty-four infants (birth weight [mean ± standard deviation, SD] 820 ± 168 g, gestational age [mean ± SD] 27.0 ± 1.6 weeks) were included in our study (12 infants started with bolus feeding and 12 with continuous feeding) and 72 histograms were obtained (36 during bolus feeding and 36 during continuous feeding). No differences in mean fraction of inspired oxygen (FiO2), and number of apnea events were observed between the two feeding modes. Oxygenation instability as assessed by time spent in different SpO2 ranges and histogram types (stable or unstable) was comparable during bolus and continuous feedings. Changing feeding mode from bolus to continuous or vice versa did not significantly change the oxygenation instability of the group, though individual infants did show a consistence response to feeding length changes. CONCLUSION: Among VLBW infants supported with NIV, oxygenation instability, as documented by SpO2 histograms, was comparable between bolus and continuous feedings. Individual infants may benefit from specific feeding length, and this can be easily demonstrated by the SpO2 histograms. KEY POINTS: · Feeding length did not affect oxygenation instability of preterm infants on noninvasive respiratory Support.. · Oxygen saturation histograms allow objective quantification of oxygenation instability at the bedside.. · Individual infants benefit from specific feeding length, as demonstrated by SpO2 histograms..

Converting qualitative data into quantitative values using a matched mixed-methods design: A new methodological approach.

BACKGROUND: Quantifying qualitative data as part of mixed-methods research (MMR) can add to the study results' analysis. Comparable results may reinforce the conclusions, while differences hold an opportunity for an in-depth discussion. To date, there is little guidance for researchers seeking to quantify their qualitative data. OBJECTIVES: Describing conversion of qualitative data to quantitative values, comparison with matched questionnaire results, discussing the benefits of this process and the matched MMR design. METHODS: We describe in detail how qualitative data from 46 interviews were converted into quantitative values (i.e., quantitative-qualitative values, QQVs) using MMR design, enabling a comparison of results from interviews and questionnaires obtained from the same participants. This process was embedded in a larger MMR study on family-caregivers caring for people-with-end-stage-dementia conducted between the years 2020-2021. RESULTS: A QQV was generated for three main themes and compared to the questionnaires' scores regarding the same topics. There were no significant differences between the scores regarding 'satisfaction with nurses and physicians care', and 'discussion with nurses and physicians about end-of-life care'. However, for 'burden', the QQV score was significantly higher than the questionnaires' score. DISCUSSION: We described how to use a matched MMR design to produce and compare QQV from interviews with questionnaire scores. This methodology may allow further valuable discussion if the results are either similar or not, and for better integration and easier presentation of the results. Comparable results can reinforce the conclusions from both parts of the MMR study, while differences hold an opportunity for an in-depth discussion regarding their meaning and context. Although we claim that this methodology can be embedded in the MMR structure and contribute significantly to the discussion's depth, it by no means replaces the traditional MMR design. PATIENT AND PUBLIC CONTRIBUTION: No patient or public contribution.

The effect of changing respiratory rate settings on CO2 levels during nasal intermittent positive pressure ventilation (NIPPV) in premature infants.

OBJECTIVE: To examine the change in CO2, when applying NIPPV with either a low or a high rate in stable premature infants. STUDY DESIGN: Prospective, controlled, crossover study. Preterm infants on NIPPV were monitored by tcCO2 during two rate changes switching every hour between high (30 bpm) and low (10 bpm) set rates. RESULTS: Fifty premature infants (mean ± SD: 28.3 ± 2.4 weeks' gestation) were enrolled. Each infant had two rate changes; therefore, a hundred rate changes were studied. The mean change in tcCO2, i.e., ΔtcCO2 (95% confidence-interval), was -1.1 (-2.3 to 0.1) mmHg for increasing rate from low to high, and 0.46 (-0.49 to 1.41) mmHg for decreasing rate from high to low. CONCLUSION: Multiplying or dividing the rate settings by three did not significantly change the tcCO2 readings an hour after the change. These findings could affect the management of ventilation settings of NIPPV in premature infants. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov ID: NCT04836689 , The name of the trial registry: "Influence of Respiratory Rate Settings on CO2 Levels During Nasal Intermittent Positive Pressure Ventilation (NIPPV)."

Oxygen saturation histogram classification system to evaluate response to doxapram treatment in preterm infants.

BACKGROUND: An oxygen saturation (SpO2) histogram classification system has been shown to enable quantification of SpO2 instability into five types, based on histogram distribution and time spent at SpO2 ≤ 80%. We aimed to investigate this classification system as a tool to describe response to doxapram treatment in infants with severe apnea of prematurity. METHODS: This retrospective study included 61 very-low-birth-weight infants who received doxapram. SpO2 histograms were generated over the 24-h before and after doxapram start. Therapy response was defined as a decrease of ≥1 histogram types after therapy start. RESULTS: The median (IQR) histogram type decreased from 4 (3-4) before to 3 (2-3) after therapy start (p < 0.001). The median (IQR) FiO2 remained constant before (27% [24-35%]) and after (26% [22-35%]) therapy. Thirty-six infants (59%) responded to therapy within 24 h. In 34/36 (94%) of the responders, invasive mechanical ventilation (IMV) was not required during the first 72 h of therapy, compared to 15/25 (60%) of non-responders (p = 0.002). Positive and negative predictive values of the 24-h response for no IMV requirement within 72 h were 0.46 and 0.94, respectively. CONCLUSIONS: Classification of SpO2 histograms provides an objective bedside measure to assess response to doxapram therapy and can serve as a tool to detect changes in oxygenation status around respiratory interventions. IMPACT: The SpO2 histogram classification system provides a tool for quantifying response to doxapram therapy. The classification system allowed estimation of the probability of invasive mechanical ventilation requirement, already within a few hours of treatment. The SpO2 histogram classification system allows an objective bedside assessment of the oxygenation status of the preterm infant, making it possible to assess the changes in oxygenation status in response to respiratory interventions.

Prenatal exposure to heavy metal mixtures and anthropometric birth outcomes: a cross-sectional study.

BACKGROUND: Numerous studies have suggested significant associations between prenatal exposure to heavy metals and newborn anthropometric measures. However, little is known about the effect of various heavy metal mixtures at relatively low concentrations. Hence, this study aimed to investigate associations between prenatal exposures to a wide range of individual heavy metals and heavy metal mixtures with anthropometric measures of newborns. METHODS: We recruited 975 mother-term infant pairs from two major hospitals in Israel. Associations between eight heavy metals (arsenic, cadmium, chromium, mercury, nickel, lead, selenium, and thallium) detected in maternal urine samples on the day of delivery with weight, length, and head circumference at birth were estimated using linear and Bayesian kernel machine regression (BKMR) models. RESULTS: Most heavy metals examined in our study were observed in lower concentrations than in other studies, except for selenium. In the linear as well as the BKMR models, birth weight and length were negatively associated with levels of chromium. Birth weight was found to be negatively associated with thallium and positively associated with nickel. CONCLUSION: By using a large sample size and advanced statistical models, we could examine the association between prenatal exposure to metals in relatively low concentrations and anthropometric measures of newborns. Chromium was suggested to be the most influential metal in the mixture, and its associations with birth weight and length were found negative. Head circumference was neither associated with any of the metals, yet the levels of metals detected in our sample were relatively low. The suggested associations should be further investigated and could shed light on complex biochemical processes involved in intrauterine fetal development.

Cardiopulmonary Exercise Testing in Childhood in Late Preterms: Comparison to Early Preterms and Term-Born Controls.

Background: Late preterm (340−366 weeks gestational age [GA]) infants may have abnormal pulmonary development and possible exercise physiology parameters. We aim to assess the effect of late prematurity on exercise capacity in childhood and to compare it to early preterm (EP) (born < 300 GA), and to term healthy control (TC) (>370 week GA). Methods: Late preterm and early preterm (7−10 years) completed a cardiopulmonary exercise test (CPET) and spirometry and were compared to EP and to TC. Results: Eighty-four children (age 9.6 ± 1.0 years, 48% girls) participated. Twenty-one former LP were compared to 38 EP (15 with Bronchopulmonary dysplasia (BPD) [EP+], 23 without BPD [EP−]) and to 25 TC children. Peak oxygen uptake (peakV̇O2) was statistically lower than in the TC, but within the normal range, and without difference from the EP (LP 90.2 ± 15.1%, TC 112.4 ± 16.9%, p < 0.001; EP+ 97.3 ± 25.5%, EP− 85.4 ± 20.8%, p = 0.016 and p < 0.001, respectively, when compared with TC). Lung function (FEV1) was lower than normal only in the EP+ (75.6 ± 14.9% predicted, compared with 12.5 ± 87.8 in EP−, 87.5 ± 16.9 in LP and 91.0 ± 11.7 in TC). Respiratory and cardiac limitations were similar between all four study groups. Conclusions: This study demonstrated lower exercise capacity (peakV̇O2) in former LP children compared with healthy term children. Exercise capacity in LP was comparable to that of EP, with and without BPD. However, the exercise test parameters, specifically peakV̇O2, were within the normal range, and no significant physiological exercise limitations were found.

Continuous versus Bolus Gastric Tube Feeding in Very Low Birth Weight Infants Supported with Noninvasive Respiratory Support: A Randomized, Pilot Study.

OBJECTIVES: This study aimed to compare time to full feeding (TFF) between continuous gastric feeding (CGF) and bolus feeding (BF) in very low birth weight (VLBW) infants supported with noninvasive ventilation (NIV) and to evaluate feasibility and identify methodological pitfalls for future large-scale studies. STUDY DESIGN: This study is a randomized controlled, prospective, pilot study. VLBW premature infants, supported with NIV, were randomized while still on trophic feeding <20 mL/kg/day to receive feeding over 2 hours of CGF or over 15- to 30-minute BF. The primary outcome was TFF. Analysis was done by intention to treat. RESULTS: Overall, 32 infants were included in this analysis, 17 in the CGF group and 15 in the BF group. Infants in the CGF group were significantly younger than the BF group (mean ± standard deviation [SD] gestational age [GA] 26.9 ± 1.2 vs. 28.9 ± 1.5 weeks, respectively). TFF was comparable with median (interquartile range [IQR]) for the two groups, 10.0 (10.0, 19.0) days in the BF group versus 12.0 (9.0, 13.0) days in the CGF group (p = 0.59). Feeding length was not found to significantly affect TFF in multivariate analysis correcting for GA. Groups were comparable in weight gain, gastrointestinal complications, length of NIV, bronchopulmonary dysplasia incidence, and age at discharge. Most infants from both groups (60% of BF and 70% of CGF) required changes in feeding length. CONCLUSION: In this pilot study, among VLBW infants supported with NIV, TFF was comparable between the BF and CGF groups. These results should be interpreted with caution due to the small sample size and despite the multivariate analysis correcting for the different GA. Interestingly, most infants required changes in feeding length regardless of their allocation. This feasibility study emphasizes the need for careful attention to randomization and strict feeding protocols including criteria for switching allocation in future large-scale studies aimed at determining the preferred feeding length during NIV in VLBW infants. KEY POINTS: · Among infants supported with NIV, length of feeding affects gastric venting.. · BF might increase gastrointestinal reflux, while continuous feeding hinders gastric decompression.. · Among infants supported by NIV, feeding tolerance was comparable between bolus and continuous groups..

Ventilation-induced epithelial injury drives biological onset of lung trauma in vitro and is mitigated with prophylactic anti-inflammatory therapeutics.

Mortality rates among patients suffering from acute respiratory failure remain perplexingly high despite the maintenance of blood oxygen homeostasis during ventilatory support. The biotrauma hypothesis advocates that mechanical forces from invasive ventilation trigger immunological mediators that spread systemically. Yet, how these forces elicit an immune response remains unclear. Here, a biomimetic in vitro three-dimensional (3D) upper airways model allows to recapitulate lung injury and immune responses induced during invasive mechanical ventilation in neonates. Under such ventilatory support, flow-induced stresses injure the bronchial epithelium of the intubated airways model and directly modulate epithelial cell inflammatory cytokine secretion associated with pulmonary injury. Fluorescence microscopy and biochemical analyses reveal site-specific susceptibility to epithelial erosion in airways from jet-flow impaction and are linked to increases in cell apoptosis and modulated secretions of cytokines IL-6, -8, and -10. In an effort to mitigate the onset of biotrauma, prophylactic pharmacological treatment with Montelukast, a leukotriene receptor antagonist, reduces apoptosis and pro-inflammatory signaling during invasive ventilation of the in vitro model. This 3D airway platform points to a previously overlooked origin of lung injury and showcases translational opportunities in preclinical pulmonary research toward protective therapies and improved protocols for patient care.

Same baby, different care: variations in practice between neonatologists and pediatric intensivists.

The aim of the study was to identify and explore areas in neonatal care in which significant differences in clinical care exist, among neonatal intensive care (NICU) and pediatric intensive care (PICU) physicians. A questionnaire presenting three common scenarios in neonatal critical care-severe pneumonia, post-cardiac-surgery care, and congenital diaphragmatic hernia (CDH) was electronically sent to all PICU and NICU physicians in Israel. The survey was completed by 110 physicians. Significant differences were noted between NICU and PICU physicians' treatment choices. A non-cuffed endotracheal tube, initial high-frequency ventilation, and lower tidal volumes when applying synchronized-intermittent-mechanical-ventilation were selected more often by NICU physicians. For sedation/analgesia, NICU physicians treated as needed or by continuous infusion of a single agent, while PICU physicians more often chose to continuously infuse ≥ 2 medications. Fentanyl, midazolam, and muscle relaxants were chosen more often by PICU physicians. Morphine administration was similar for both groups. Treating CDH with pulmonary hypertension and systemic hypotension, NICU physicians more often began treatment with high dose dopamine and/or dobutamine, while PICU physicians chose low-dose adrenalin and/or milrinone. For vascular access NICU physicians chose umbilical lines most often, while PICU physicians preferred other central sites. CONCLUSION: Our study identified major differences in respiratory and hemodynamic care, sedation and analgesia, and vascular access between NICU and PICU physicians, resulting from field-specific consensus guidelines and practice traditions. We suggest to establish joint committees from both professions, aimed at finding the optimal treatment for this vulnerable population - be it in the NICU or in the PICU. WHAT IS KNOWN: • Variability in neonatal care between the neonatal and the pediatric intensive care units has been previously described. WHAT IS NEW: • This scenario-based survey study identified major differences in respiratory and hemodynamic care, sedation and analgesia, and vascular access between neonatologists and pediatric intensivists, resulting from lack of evidence-based literature to guide neonatal care, field-specific consensus guidelines, and practice traditions. • These findings indicate a need for joint committees, combining the unique skills and literature from both professions, to conduct clinical trials focusing on these specific areas of care, aimed at finding the optimal treatment for this vulnerable population - be it in the neonatal or the pediatric intensive care unit.

Secondary Traumatic Stress and Vigor Among Neonatal Intensive Care Unit Personnel: The Moderator Role of Coping Flexibility.

BACKGROUND: The demanding and highly stressful work environment of the neonatal intensive care unit (NICU) has led to the identification of a possible psychological stress reaction among NICU nurses and physicians, termed secondary traumatic stress (STS). PURPOSE: The current study aimed to explore the association between vigor at work (as an energy resource) and STS, while considering their association with the professional role (nurses/physicians-as a condition resource) as well as with coping flexibility (as a personal resource). METHODS: In this cross-sectional study physicians and nurses working in NICUs across Israel completed a questionnaire comprising sections on demographics and professional characteristics, self-rated health, STS, coping flexibility, and vigor. RESULTS: Of 280 physicians and nurses approached, 70% (195) completed the questionnaire. No significant differences between nurses and physicians were found in STS adjusted for gender, being in a committed relationship, and seniority in the NICU. Vigor was negatively correlated with STS-both in the entire sample and for each professional role alone. Coping flexibility was a statistically significant moderator between vigor and STS, whereas the interaction between vigor and professional role was not significant. Specifically, the negative relationship between vigor and STS was significant when coping flexibility was more than 10.10 (61% of the participants) but not significant at lower values. IMPLICATIONS FOR PRACTICE AND RESEARCH: The understanding of the relationship between vigor and STS, with coping flexibility as its moderator, encourages an intervention aimed at reducing stress by increasing these resources.

Rapid methicillin resistance diversification in Staphylococcus epidermidis colonizing human neonates.

Early in life, infants are colonized with multiple bacterial strains whose differences in gene content can have important health consequences. Metagenomics-based approaches have revealed gene content differences between different strains co-colonizing newborns, but less is known about the rate, mechanism, and phenotypic consequences of gene content diversification within strains. Here, focusing on Staphylococcus epidermidis, we whole-genome sequence and phenotype more than 600 isolates from newborns. Within days of birth, infants are co-colonized with a highly personalized repertoire of S. epidermidis strains, which are spread across the newborn body. Comparing the genomes of multiple isolates of each strain, we find very little evidence of adaptive evolution via single-nucleotide polymorphisms. By contrast, we observe gene content differences even between otherwise genetically identical cells, including variation of the clinically important methicillin resistance gene, mecA, suggesting rapid gene gain and loss events at rates higher than point mutations. Mapping the genomic architecture of structural variants by long-read Nanopore sequencing, we find that deleted regions were always flanked by direct repeats, consistent with site-specific recombination. However, we find that even within a single genetic background, recombination occurs at multiple, often non-canonical repeats, leading to the rapid evolution of patient-specific diverse structural variants in the SCCmec island and to differences in antibiotic resistance.

Respiratory morbidity in very low birth weight infants through childhood and adolescence.

OBJECTIVE: To describe the long-term (up to 18 years of age) respiratory outcomes of children and adolescents born at very low birth weight (VLBW; ≤1500 g) in comparison with that of children born >1500 g. METHODS: An observational, longitudinal, retrospective study comparing VLBW infants with matched controls, registered at a large health maintenance organization in Israel. Pulmonary outcomes collected anonymously from the electronic medical files included respiratory illness diagnoses, purchased medications for respiratory problems, office visits with either a pediatric pulmonologist or cardiologist and composite respiratory morbidity combining all these parameters. RESULTS: Our study included 5793 VLBW infants and 11,590 matched controls born between 1998 and 2012. The majority (99%) of VLBW infants were premature (born < 37 weeks' gestation), while 93% of controls were born at term. The composite respiratory morbidity was significantly higher in VLBW infants compared with controls in all age groups (relative risk [95% confidence interval]: 1 year: 1.22 [1.19-1.26], <2 years: 1.30 [1.27-1.34], 2-6 years: 1.29 [1.27-1.32], 6-12 years: 1.53 [1.47-1.59], 12-18 years: 1.46 [1.35-1.56]; respectively). Both VLBW infants and controls demonstrated a steady decline in the composite respiratory morbidity with aging. In VLBW infants, lower gestational age was associated with higher respiratory morbidity only until 2 years of age and the morbidity declined in each gestational age group until adolescence. CONCLUSION: Our study confirmed a strong association between VLBW and pulmonary morbidity. The higher prevalence of respiratory composite morbidity in VLBW infants persists over the years until adolescence. The respiratory morbidity is most evident in the first year of life and declines afterward.

Evaluation of audio-voice guided application for neonatal resuscitation: a prospective, randomized, pilot study.

OBJECTIVES: To examine whether audio-voice guidance application improves adherence to resuscitation sequence and recommended time frames during neonatal resuscitation. METHODS: A prospective, randomized, pilot study examining the use of an audio-voice application for guiding resuscitation on newborn mannequins, based on the Neonatal Resuscitation Program (NRP) algorithm. Two different scenarios, with and without voice guidance, were presented to 20 medical personnel (2 midwives, 8 nurses, and 10 physicians) in random order, and their performance videotaped. RESULTS: Audio-voice guided resuscitation compared with non-guided resuscitation, resulted in significantly better compliance with NRP order sequence (p<0.01), correct use of oxygen supplementation (p<0.01) and performance of MR SOPA (Mask, reposition, suction, open mouth, pressure, airway) (p<0.01), and shortened the time to "positive pressure ventilation" (p<0.01). CONCLUSIONS: In this pilot study, audio-voice guidance application for newborn resuscitation simulation on mannequins, based on the NRP algorithm, improved adherence and performance of NRP guidelines.

Cannula With Long and Narrow Tubing vs Short Binasal Prongs for Noninvasive Ventilation in Preterm Infants: Noninferiority Randomized Clinical Trial.

Importance: Use of cannulas with long and narrow tubing (CLNT) has gained increasing popularity for applying noninvasive respiratory support for newborn infants thanks to ease of use, perceived patient comfort, and reduced nasal trauma. However, there is concern that this interface delivers reduced and suboptimal support. Objective: To determine whether CLNT is noninferior to short binasal prongs and masks (SPM) when providing nasal intermittent positive pressure ventilation (NIPPV) in preterm infants. Design, Setting, and Participants: This randomized controlled, unblinded, prospective noninferiority trial was conducted between December 2017 and December 2019 at 2 tertiary neonatal intensive care units. Preterm infants born between 24 weeks' and 33 weeks and 6 days' gestation were eligible if presented with respiratory distress syndrome with the need for noninvasive ventilatory support either as initial treatment after birth or after first extubation. Analysis was performed by intention to treat. Interventions: Randomization to NIPPV with either CLNT or SPM interface. Main Outcomes and Measures: The primary outcome was the need for intubation within 72 hours after NIPPV treatment began. Noninferiority margin was defined as 15% or less absolute difference. Results: Overall, 166 infants were included in this analysis, and infant characteristics and clinical condition (including fraction of inspired oxygen, Pco2, and pH level) were comparable at recruitment in the CLNT group (n = 83) and SPM group (n = 83). The mean (SD) gestational age was 29.3 (2.2) weeks vs 29.2 (2.5) weeks, and the mean (SD) birth weight was 1237 (414) g vs 1254 (448) g in the CLNT and SPM groups, respectively. Intubation within 72 hours occurred in 12 of 83 infants (14%) in the CLNT group and in 15 of 83 infants (18%) in the SPM group (risk difference, -3.6%; 95% CI, -14.8 to 7.6 [within the noninferiority margin], χ2 P = .53). Moderate to severe nasal trauma was significantly less common in the CLNT group compared with the SPM group (4 [5%] vs 14 [17%]; P = .01). There were no differences in other adverse events or in the course during hospitalization. Conclusions and Relevance: In this study, CLNT was noninferior to SPM in providing NIPPV for preterm infants, while causing significantly less nasal trauma. Trial Registration: ClinicalTrials.gov Identifier: NCT03081611.

[ALTERATIONS IN SENSITIVE MEASURES OF CARDIAC FUNCTION IN HEALTHY NEONATES DURING PHOTOTHERAPY].

OBJECTIVES: Phototherapy has been reported to reduce coronary blood flow in neonates but without affecting gross measures of cardiac function. The aim of our current study was to evaluate earlier, more sensitive changes in cardiac function during phototherapy. METHODS: Nineteen neonates with jaundice treated with phototherapy had Doppler echocardiographic evaluation, before, during and after phototherapy and were compared to 25 matched controls. Sensitive measures for cardiac performance in this study included left ventricular dimension, ventricular Doppler parameters and regional function assessment. RESULTS: Phototherapy was associated with a significant increase in heart rate. In addition, atrioventricular valve closure to opening interval decreased significantly during phototherapy while ventricular ejection times tended to decrease. However, left and right ventricular filling parameters and outflow velocity parameters, longitudinal tissue-Doppler annular velocities and myocardial performance indices were not affected by phototherapy and were similar to those in controls. Coronary blood velocities and integrals decreased significantly during phototherapy. CONCLUSIONS: Our study found no differences in early and sensitive measures of cardiac performance including the diastolic and systolic function, despite modestly lower flow in coronary arteries among healthy neonates during phototherapy.