Prophylactic Oropharyngeal Surfactant for Preterm Newborns at Birth: A Randomized Clinical Trial.

Importance: Preterm newborns at risk of respiratory distress syndrome are supported with continuous positive airway pressure (CPAP). Many newborns worsen despite CPAP and are intubated for surfactant administration, an effective therapy for treatment of respiratory distress syndrome. Endotracheal intubation is associated with adverse effects. Pharyngeal administration of surfactant to preterm animals and humans has been reported as an alternative. Objective: To assess whether giving prophylactic oropharyngeal surfactant to preterm newborns at birth would reduce the rate of intubation for respiratory failure. Design, Setting, and Participants: This unblinded, parallel-group randomized clinical trial (Prophylactic Oropharyngeal Surfactant for Preterm Infants [POPART]) was conducted from December 17, 2017, to September 11, 2020, at 9 tertiary neonatal intensive care units in 6 European countries. Newborns born before 29 weeks of gestation without severe congenital anomalies, for whom intensive care was planned, were eligible for inclusion. The data were analyzed from July 27, 2022, to June 20, 2023. Intervention: Newborns were randomly assigned to receive oropharyngeal surfactant at birth in addition to CPAP or CPAP alone. Randomization was stratified by center and gestational age (GA). Main Outcomes and Measures: The primary outcome was intubation in the delivery room for bradycardia and/or apnea or in the neonatal intensive care unit for prespecified respiratory failure criteria within 120 hours of birth. Caregivers were not masked to group assignment. Results: Among 251 participants (mean [SD] GA, 26 [1.5] weeks) who were well matched at study entry, 126 (69 [54.8%] male) with a mean (SD) birth weight of 858 (261) grams were assigned to the oropharyngeal surfactant group, and 125 (63 [50.4%] male) with a mean (SD) birth weight of 829 (253) grams were assigned to the control group. The proportion of newborns intubated within 120 hours was not different between the groups (80 [63.5%) in the oropharyngeal surfactant group and 81 [64.8%] in the control group; relative risk, 0.98 [95% CI, 0.81-1.18]). More newborns assigned to the oropharyngeal surfactant group were diagnosed with and treated for pneumothorax (21 [16.6%] vs 8 [6.4%]; P = .04). Conclusions and Relevance: This randomized clinical trial found that administration of prophylactic oropharyngeal surfactant to newborns born before 29 weeks' GA did not reduce the rate of intubation in the first 120 hours of life. These findings suggest that administration of surfactant into the oropharynx immediately after birth in addition to CPAP should not be routinely used. Trial Registration: EudraCT: 2016-004198-41.

Research in the Delivery Room: Can You Tell Me It's Evolution?

Many of the recommendations for newborn care in the delivery room (DR) are based on retrospective observational studies, preclinical studies of mannequins or animal models, and expert opinion. Conducting DR research is challenging. Many deliveries occur in fraught circumstances with little prior warning, making it difficult to get prospective consent from parents and buy-in from clinicians. Many DR interventions are difficult to mask for the purpose of a clinical trial and it is not easy to identify appropriate outcomes for studies that are sufficiently "short-term" that they are likely to be influenced by the intervention, yet sufficiently "long-term" to be considered clinically important. However, despite these challenges, much information has been accrued from clinical studies in recent years. In this article, we outline our experience of conducting clinical research in the DR. In our initial studies almost 20 years ago, we found wide variation in the equipment used both nationally and internationally, reflecting the paucity of evidence to support practice. This started a journey that has included many observational studies and randomized controlled trials that have attempted to refine how we care for newborn infants in the DR. Each has given further information and, inevitably, raised many more questions about the approach to caring for newborns in the DR.

Tensor-structured decomposition improves systems serology analysis.

Systems serology provides a broad view of humoral immunity by profiling both the antigen-binding and Fc properties of antibodies. These studies contain structured biophysical profiling across disease-relevant antigen targets, alongside additional measurements made for single antigens or in an antigen-generic manner. Identifying patterns in these measurements helps guide vaccine and therapeutic antibody development, improve our understanding of diseases, and discover conserved regulatory mechanisms. Here, we report that coupled matrix-tensor factorization (CMTF) can reduce these data into consistent patterns by recognizing the intrinsic structure of these data. We use measurements from two previous studies of HIV- and SARS-CoV-2-infected subjects as examples. CMTF outperforms standard methods like principal components analysis in the extent of data reduction while maintaining equivalent prediction of immune functional responses and disease status. Under CMTF, model interpretation improves through effective data reduction, separation of the Fc and antigen-binding effects, and recognition of consistent patterns across individual measurements. Data reduction also helps make prediction models more replicable. Therefore, we propose that CMTF is an effective general strategy for data exploration in systems serology.

Randomised study of heart rate measurement in preterm newborns with ECG plus pulse oximetry versus oximetry alone.

AIM: To determine whether the IntelliVue monitor (ECG plus Masimo pulse oximeter (PO)) displays heart rate (HR) at birth more quickly than Nellcor PO (PO alone) among infants of 29-35 weeks' gestational age. METHODS: Unmasked parallel group randomised (1:1) study. RESULTS: We planned to enrol 100 infants; however, the study was terminated due to the COVID-19 pandemic when 39 infants had been enrolled (17 randomised to IntelliVue, 22 to Nellcor). We found no differences between the groups in the time to first HR display (median (IQR) IntelliVue ECG 49 (33, 71) vs Nellcor 47 (37, 86) s, p>0.999), in the proportion who had a face mask applied for breathing support, or in the time at which it was applied. Infants monitored with IntelliVue were handled more frequently and for longer. CONCLUSION: IntelliVue ECG did not display HR more quickly than Nellcor PO in preterm infants. We found no differences in the rate of or time to intervention between groups. Our study was terminated early so these findings should be interpreted with caution. TRIAL REGISTRATION NUMBER: ISRCTN16473881.

Initiation of respiratory support for extremely preterm infants at birth.

Neonatal resuscitation algorithms recommend assessing breathing and heart rate (HR) of newborns and giving respiratory support when one or both are unsatisfactory. Recommendations also state that preterm infants may be supported with continuous positive airway pressure rather than routinely intubated for positive pressure ventilation (PPV). We wished to describe the prevalence and time of initiation of respiratory support of extremely preterm and extremely low birthweight (ELBW) infants at our hospital. We reviewed videos of 55 infants. Although most were breathing, practically all newly born extremely preterm ELBW infants were given respiratory support soon after arrival to the resuscitation cot. For the majority, this was done without knowing the HR. The majority received PPV; again, this was often done without knowing the HR. A quarter of infants were managed without any PPV.

Crying and breathing by new-born preterm infants after early or delayed cord clamping.

Guidelines recommend delayed cord clamping (DCC) of at least 30 s for vigorous preterm infants who do not require resuscitation. It is not known whether DCC affects the rate of crying and breathing after birth. We reviewed videos of 80 preterm infants in the delivery room. Most infants cried and breathed after both immediate and delayed cord clamping before respiratory support was given. Infants arrived at the resuscitaire in similar physiological condition, regardless of the time after birth at which they arrived.

Randomised trial of estimating oral endotracheal tube insertion depth in newborns using suprasternal palpation of the tip or weight.

BACKGROUND: Endotracheal tube (ETT) tip position is determined on chest X-ray (CXR) and should lie between the upper border of the first thoracic vertebra (T1) and the lower border of second thoracic vertebra (T2). Infant weight is commonly used to estimate how far the ETT should be inserted but frequently results in malpositioned ETT tips. Palpation of the ETT tip at the suprasternal notch has been recommended as an alternative. OBJECTIVE: To determine whether estimating ETT insertion depth using suprasternal palpation of the ETT tip rather than weight results in more correctly positioned ETT tips. DESIGN: Single-centre randomised controlled trial. SETTING: Level III neonatal intensive care unit (NICU) at a university maternity hospital. PATIENTS: Newborn infants without congenital anomalies intubated in the NICU. INTERVENTIONS: Participants were randomised to have ETT insertion depth estimated using palpation of the ETT tip at the suprasternal notch or weight [insertion depth (cm)=6 + wt (kg)]. MAIN OUTCOME MEASURE: Correct ETT position, that is, between the upper border of T1 and lower border of T2 on CXR, determined by one consultant paediatric radiologist masked to group assignment. RESULTS: There was no difference in the proportion of correctly placed ETT tips between the groups (suprasternal palpation 27/58 (47%) vs weight 23/60 (38%), p=0.456). Most incorrectly positioned ETTs were too low (56/68 (82%)). CONCLUSION: Estimating ETT insertion depth using suprasternal palpation did not result in more correctly positioned ETTs. TRIAL REGISTRATION NUMBER: ISRCTN13570106.

Randomised study comparing heart rate measurement in newly born infants using a monitor incorporating electrocardiogram and pulse oximeter versus pulse oximeter alone.

AIM: To determine whether IntelliVue (ECG plus Masimo pulse oximeter (PO)) measures heart rate (HR) in low-risk newborns more quickly than Nellcor PO (PO alone). METHODS: Unmasked parallel group randomised (1:1) study. RESULTS: We studied 100 infants, 47 randomised to IntelliVue, 53 to Nellcor. Time to first HR was shorter with IntelliVue ECG than Nellcor (median (IQR) 24 (19, 39) vs 48 (36, 69) s, p<0.001). There was no difference in time to display both HR and SpO2 (52 (47, 76) vs 48 (36, 69) s, p=0.507). IntelliVue PO displayed initial bradycardia more often than the Nellcor (55% vs 6%). Infants monitored with IntelliVue were handled more frequently and for longer. CONCLUSIONS: IntelliVue ECG displayed HR more quickly than Nellcor PO. IntelliVue PO often displayed initial bradycardia. Infants monitored with IntelliVue were handled more often. Study of ECG in high-risk infants is warranted.

Effect of Needle Aspiration of Pneumothorax on Subsequent Chest Drain Insertion in Newborns: A Randomized Clinical Trial.

Importance: Treatment options for a symptomatic pneumothorax in newborns include needle aspiration (NA) and chest drain (CD) insertion. There is little consensus as to the preferred treatment, reflecting a lack of evidence from clinical trials. Objective: To investigate whether treating pneumothoraces diagnosed on chest radiography (CR) in newborns receiving respiratory support with NA results in fewer infants having CDs inserted within 6 hours of diagnosis. Design, Setting, and Participants: This randomized clinical trial was conducted from October 7, 2013, to December 21, 2016. The setting was 5 tertiary European neonatal intensive care units. Infants receiving respiratory support (endotracheal ventilation, continuous positive airway pressure, or supplemental oxygen >40%) who had a pneumothorax on CR that clinicians deemed needed treatment were eligible for inclusion. Interventions: Infants were randomly assigned (1:1) to drainage using NA or CD insertion, stratified by center and gestation at birth (<32 vs ≥32 weeks). Caregivers were not masked to group assignment. For NA, a needle was inserted between the ribs to aspirate air and was removed once air was no longer aspirated. A CD was inserted if clinicians deemed that the response was inadequate. For CD insertion, a drain was inserted between the ribs and was left in situ. Main Outcomes and Measures: The primary outcome was whether a CD was inserted on the side of the pneumothorax within 6 hours of diagnosis. Results: A total of 76 infants were randomly assigned, and 6 (4 assigned to NA and 2 to CD) were excluded because they met exclusion criteria at enrollment. Of the 70 remaining infants, 33 (16 male [48%]) were assigned to NA and 37 (22 male [59%]) to CD insertion. Their median (interquartile range [IQR]) gestational age was 31 (27-38) vs 31 (27-35) weeks, and their median (IQR) birth weight was 1385 (1110-3365) vs 1690 (1060-2025) g, respectively. Fewer infants assigned to NA had a CD inserted within 6 hours (55% [18 of 33] vs 100% [37 of 37]; relative risk, 0.55; 95% CI, 0.40-0.75) and during hospitalization (70% [23 of 33] vs 100% [37 of 37]; relative risk, 0.70, 95% CI, 0.56-0.87). Conclusions and Relevance: Needle aspiration reduced the rate of CD insertion in symptomatic newborns with pneumothorax on CR. It should be used as the initial method of draining radiologically confirmed pneumothorax in symptomatic infants. Trial Registration: isrctn.org Identifier: ISRCTN65161530.

Comparison of infant heart rate assessment by auscultation, ECG and oximetry in the delivery room.

Clinical assessment of an infant's heart rate (HR) in the delivery room (DR) has been reported to be inaccurate. We compared auscultation of the HR using a stethoscope with electrocardiography (ECG) and pulse oximetry (PO) for determining the HR in 92 low-risk newborn infants in the DR. Caregivers auscultated the HR while masked to the HR on the monitor. Auscultation underestimated ECG HR (mean difference (95% CI) by -9 (-15 to -2) beats per minute (bpm)) and PO HR (mean difference (95% CI) by -5 (-12 to 2) bpm). The median (IQR) time to HR by auscultation was 14 (10-18) s. As HR was determined quickly and with reasonable accuracy by auscultation in low-risk newborns, study in high-risk infants is warranted.

Randomised trial of estimating oral endotracheal tube insertion depth in newborns using weight or vocal cord guide.

BACKGROUND: When intubating newborns, clinicians aim to position the endotracheal tube (ETT) tip in the midtrachea. The depth to which ETTs should be inserted is often estimated using the infant's weight. ETTs are frequently incorrectly positioned in newborns, most often inserted too far. Using the vocal cord guide (a mark at the distal end of the ETT) to guide insertion depth has been recommended. OBJECTIVE: To determine whether estimating ETT insertion depth using the vocal cord guide rather than weight results in more correctly positioned ETT tips. DESIGN: Single-centre randomised controlled trial. SETTING: Level III neonatal intensive care unit (NICU) at a university maternity hospital (National Maternity Hospital, Dublin, Ireland). PATIENTS: Newborn infants without congenital anomalies intubated in the NICU. INTERVENTIONS: Participants were randomised to have ETT insertion depth estimated using weight [insertion depth (cm) = weight (kg) +6] or vocal cord guide. MAIN OUTCOME MEASURE: Correct ETT position, that is, tip between the upper border of the first thoracic vertebra (T1) and the lower border of the second thoracic vertebra (T2) on a chest X-ray as determined by one paediatric radiologist masked to group assignment. RESULTS: 136 participants were randomised. The proportion of correctly positioned ETTs was similar in both groups (weight 30/69 (44%) vs vocal cord guide 27/67 (40%), p=0.731). Most incorrectly positioned ETT (69/79, 87%) were too low. CONCLUSION: Estimating ETT insertion depth using the vocal cord guide did not result in more correctly positioned ETT tips. TRIAL REGISTRATION NUMBER: ISRCTN39654846.