Two-Year Outcomes After Minimally Invasive Surfactant Therapy in Preterm Infants: Follow-Up of the OPTIMIST-A Randomized Clinical Trial.

Importance: The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified. Objective: To examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years' corrected age. Design, Setting, and Participants: Follow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries. The trial included 486 infants with a gestational age of 25 to 28 weeks supported with continuous positive airway pressure (CPAP). Collection of follow-up data at 2 years' corrected age was completed on December 9, 2022. Interventions: Infants assigned to MIST (n = 242) received exogenous surfactant (200 mg/kg poractant alfa) via a thin catheter; those assigned to the control group (n = 244) received sham treatment. Main Outcomes and Measures: The key secondary outcome of death or moderate to severe NDD was assessed at 2 years' corrected age. Other secondary outcomes included components of this composite outcome, as well as hospitalizations for respiratory illness and parent-reported wheezing or breathing difficulty in the first 2 years. Results: Among the 486 infants randomized, 453 had follow-up data available (median gestation, 27.3 weeks; 228 females [50.3%]); data on the key secondary outcome were available in 434 infants. Death or NDD occurred in 78 infants (36.3%) in the MIST group and 79 (36.1%) in the control group (risk difference, 0% [95% CI, -7.6% to 7.7%]; relative risk [RR], 1.0 [95% CI, 0.81-1.24]); components of this outcome did not differ significantly between groups. Secondary respiratory outcomes favored the MIST group. Hospitalization with respiratory illness occurred in 49 infants (25.1%) in the MIST group vs 78 (38.2%) in the control group (RR, 0.66 [95% CI, 0.54-0.81]) and parent-reported wheezing or breathing difficulty in 73 (40.6%) vs 104 (53.6%), respectively (RR, 0.76 [95% CI, 0.63-0.90]). Conclusions and Relevance: In this follow-up study of a randomized clinical trial of preterm infants with respiratory distress syndrome supported with CPAP, MIST compared with sham treatment did not reduce the incidence of death or NDD by 2 years of age. However, infants who received MIST had lower rates of adverse respiratory outcomes during their first 2 years of life. Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943.

Implementation of a Standardized Neonatal Intubation Training Package.

OBJECTIVE: To assess the first attempt neonatal intubation success rates of pediatric trainees following the implementation of an evidence-based training package. STUDY DESIGN: Data collection was undertaken from February, 1 2017, to January 31, 2018, to ascertain baseline preimplementation intubation success rates. An intubation training package, which included the use of videolaryngoscopy, preprocedure pause, and standardized instruction during the procedure, was introduced. Data on all subsequent intubations were collected prospectively from May 1, 2018, to April 30, 2020. RESULTS: Preimplementation baseline data over a 1-year period demonstrated overall first attempt intubation success rate of junior trainees to be 37% (33/89). After implementation of the training package, 290 intubations were analyzed over a 2-year period. The overall success rate was 67% (194/290); 61% (117/192) for junior trainees and 79% (77/98) for senior clinicians. Three or more attempts were required for 13% of intubations (38/290). During the study period, the overall number of intubations being carried out decreased. Intubations with the videolaryngoscope had higher success rates for all tiers of clinician, most marked in the junior tiers. CONCLUSIONS: The introduction of a standardized intubation training package, along with videolaryngoscopy, improved trainee intubation success rates.

Effect of Minimally Invasive Surfactant Therapy vs Sham Treatment on Death or Bronchopulmonary Dysplasia in Preterm Infants With Respiratory Distress Syndrome: The OPTIMIST-A Randomized Clinical Trial.

Importance: The benefits of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome are uncertain. Objective: To examine the effect of selective application of MIST at a low fraction of inspired oxygen threshold on survival without bronchopulmonary dysplasia (BPD). Design, Setting, and Participants: Randomized clinical trial including 485 preterm infants with a gestational age of 25 to 28 weeks who were supported with continuous positive airway pressure (CPAP) and required a fraction of inspired oxygen of 0.30 or greater within 6 hours of birth. The trial was conducted at 33 tertiary-level neonatal intensive care units around the world, with blinding of the clinicians and outcome assessors. Enrollment took place between December 16, 2011, and March 26, 2020; follow-up was completed on December 2, 2020. Interventions: Infants were randomized to the MIST group (n = 241) and received exogenous surfactant (200 mg/kg of poractant alfa) via a thin catheter or to the control group (n = 244) and received a sham (control) treatment; CPAP was continued thereafter in both groups unless specified intubation criteria were met. Main Outcomes and Measures: The primary outcome was the composite of death or physiological BPD assessed at 36 weeks' postmenstrual age. The components of the primary outcome (death prior to 36 weeks' postmenstrual age and BPD at 36 weeks' postmenstrual age) also were considered separately. Results: Among the 485 infants randomized (median gestational age, 27.3 weeks; 241 [49.7%] female), all completed follow-up. Death or BPD occurred in 105 infants (43.6%) in the MIST group and 121 (49.6%) in the control group (risk difference [RD], -6.3% [95% CI, -14.2% to 1.6%]; relative risk [RR], 0.87 [95% CI, 0.74 to 1.03]; P = .10). Incidence of death before 36 weeks' postmenstrual age did not differ significantly between groups (24 [10.0%] in MIST vs 19 [7.8%] in control; RD, 2.1% [95% CI, -3.6% to 7.8%]; RR, 1.27 [95% CI, 0.63 to 2.57]; P = .51), but incidence of BPD in survivors to 36 weeks' postmenstrual age was lower in the MIST group (81/217 [37.3%] vs 102/225 [45.3%] in the control group; RD, -7.8% [95% CI, -14.9% to -0.7%]; RR, 0.83 [95% CI, 0.70 to 0.98]; P = .03). Serious adverse events occurred in 10.3% of infants in the MIST group and 11.1% in the control group. Conclusions and Relevance: Among preterm infants with respiratory distress syndrome supported with CPAP, minimally invasive surfactant therapy compared with sham (control) treatment did not significantly reduce the incidence of the composite outcome of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age. However, given the statistical uncertainty reflected in the 95% CI, a clinically important effect cannot be excluded. Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943.

Frenotomy for tongue-tie in newborn infants.

BACKGROUND: Tongue-tie, or ankyloglossia, is a condition whereby the lingual frenulum attaches near the tip of the tongue and may be short, tight and thick. Tongue-tie is present in 4% to 11% of newborns. Tongue-tie has been cited as a cause of poor breastfeeding and maternal nipple pain. Frenotomy, which is commonly performed, may correct the restriction to tongue movement and allow more effective breastfeeding with less maternal nipple pain. OBJECTIVES: To determine whether frenotomy is safe and effective in improving ability to feed orally among infants younger than three months of age with tongue-tie (and problems feeding).Also, to perform subgroup analysis to determine the following.• Severity of tongue-tie before frenotomy as measured by a validated tool (e.g. Hazelbaker Assessment Tool for Lingual Frenulum Function (ATLFF) scores < 11; scores ≥ 11) (Hazelbaker 1993).• Gestational age at birth (< 37 weeks' gestation; 37 weeks' gestation and above).• Method of feeding (breast or bottle).• Age at frenotomy (≤ 10 days of age; > 10 days to three months of age).• Severity of feeding difficulty (infants with feeding difficulty affecting weight gain (as assessed by infant's not regaining birth weight by day 14 or falling off centiles); infants with symptomatic feeding difficulty but thriving (greater than birth weight by day 14 and tracking centiles). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and CINAHL up to January 2017, as well as previous reviews including cross-references, expert informants and journal handsearching. We searched clinical trials databases for ongoing and recently completed trials. We applied no language restrictions. SELECTION CRITERIA: Randomised, quasi-randomised controlled trials or cluster-randomised trials that compared frenotomy versus no frenotomy or frenotomy versus sham procedure in newborn infants. DATA COLLECTION AND ANALYSIS: Review authors extracted from the reports of clinical trials data regarding clinical outcomes including infant feeding, maternal nipple pain, duration of breastfeeding, cessation of breastfeeding, infant pain, excessive bleeding, infection at the site of frenotomy, ulceration at the site of frenotomy, damage to the tongue and/or submandibular ducts and recurrence of tongue-tie. We used the GRADE approach to assess the quality of evidence. MAIN RESULTS: Five randomised trials met our inclusion criteria (n = 302). Three studies objectively measured infant breastfeeding using standardised assessment tools. Pooled analysis of two studies (n = 155) showed no change on a 10-point feeding scale following frenotomy (mean difference (MD) -0.1, 95% confidence interval (CI) -0.6 to 0.5 units on a 10-point feeding scale). A third study (n = 58) showed objective improvement on a 12-point feeding scale (MD 3.5, 95% CI 3.1 to 4.0 units of a 12-point feeding scale). Four studies objectively assessed maternal pain. Pooled analysis of three studies (n = 212) based on a 10-point pain scale showed a reduction in maternal pain scores following frenotomy (MD -0.7, 95% CI -1.4 to -0.1 units on a 10-point pain scale). A fourth study (n = 58) also showed a reduction in pain scores on a 50-point pain scale (MD -8.6, 95% CI -9.4 to -7.8 units on a 50-point pain scale). All studies reported no adverse effects following frenotomy. These studies had serious methodological shortcomings. They included small sample sizes, and only two studies blinded both mothers and assessors; one did not attempt blinding for mothers nor for assessors. All studies offered frenotomy to controls, and most controls underwent the procedure, suggesting lack of equipoise. No study was able to report whether frenotomy led to long-term successful breastfeeding. AUTHORS' CONCLUSIONS: Frenotomy reduced breastfeeding mothers' nipple pain in the short term. Investigators did not find a consistent positive effect on infant breastfeeding. Researchers reported no serious complications, but the total number of infants studied was small. The small number of trials along with methodological shortcomings limits the certainty of these findings. Further randomised controlled trials of high methodological quality are necessary to determine the effects of frenotomy.

Orotracheal intubation in infants performed with a stylet versus without a stylet.

BACKGROUND: Neonatal endotracheal intubation is a common and potentially life-saving intervention. It is a mandatory skill for neonatal trainees, but one that is difficult to master and maintain. Intubation opportunities for trainees are decreasing and success rates are subsequently falling. Use of a stylet may aid intubation and improve success. However, the potential for associated harm must be considered. OBJECTIVES: To compare the benefits and harms of neonatal orotracheal intubation with a stylet versus neonatal orotracheal intubation without a stylet. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE; Embase; the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and previous reviews. We also searched cross-references, contacted expert informants, handsearched journals, and looked at conference proceedings. We searched clinical trials registries for current and recently completed trials. We conducted our most recent search in April 2017. SELECTION CRITERIA: All randomised, quasi-randomised, and cluster-randomised controlled trials comparing use versus non-use of a stylet in neonatal orotracheal intubation. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed results of searches against predetermined criteria for inclusion, assessed risk of bias, and extracted data. We used the standard methods of the Cochrane Collaboration, as documented in the Cochrane Handbook for Systemic Reviews of Interventions, and of the Cochrane Neonatal Review Group. MAIN RESULTS: We included a single-centre non-blinded randomised controlled trial that reported a total of 302 intubation attempts in 232 infants. The median gestational age of enrolled infants was 29 weeks. Paediatric residents and fellows performed the intubations. We judged the study to be at low risk of bias overall. Investigators compared success rates of first-attempt intubation with and without use of a stylet and reported success rates as similar between stylet and no-stylet groups (57% and 53%) (P = 0.47). Success rates did not differ between groups in subgroup analyses by provider level of training and infant weight. Results showed no differences in secondary review outcomes, including duration of intubation, number of attempts, participant instability during the procedure, and local airway trauma. Only 25% of all intubations took less than 30 seconds to perform. Study authors did not report neonatal morbidity nor mortality. We considered the quality of evidence as low on GRADE analysis, given that we identified only one unblinded study. AUTHORS' CONCLUSIONS: Current available evidence suggests that use of a stylet during neonatal orotracheal intubation does not significantly improve the success rate among paediatric trainees. However, only one brand of stylet and one brand of endotracheal tube have been tested, and researchers performed all intubations on infants in a hospital setting. Therefore, our results cannot be generalised beyond these limitations.

Endotracheal Tube Size Adjustments Within Seven Days of Neonatal Intubation.

BACKGROUND AND OBJECTIVES: Neonatal endotracheal tube (ETT) size recommendations are based on limited evidence. We sought to determine data-driven weight-based ETT sizes for infants undergoing tracheal intubation and to compare these with Neonatal Resuscitation Program (NRP) recommendations. METHODS: Retrospective multicenter cohort study from an international airway registry. We evaluated ETT size changes (downsizing to a smaller ETT during the procedure or upsizing to a larger ETT within 7 days) and risk of procedural adverse outcomes associated with first-attempt ETT size selection when stratifying the cohort into 200 g subgroups. RESULTS: Of 7293 intubations assessed, the initial ETT was downsized in 5.0% of encounters and upsized within 7 days in 1.5%. ETT downsizing was most common when NRP-recommended sizes were attempted in the following weight subgroups: 1000 to 1199 g with a 3.0 mm (12.6%) and 2000 to 2199 g with a 3.5 mm (17.1%). For infants in these 2 weight subgroups, selection of ETTs 0.5 mm smaller than NRP recommendations was independently associated with lower odds of adverse outcomes compared with NRP-recommended sizes. Among infants weighing 1000 to 1199 g: any tracheal intubation associated event, 20.8% with 2.5 mm versus 21.9% with 3.0 mm (adjusted OR [aOR] 0.62, 95% confidence interval [CI] 0.41-0.94); severe oxygen desaturation, 35.2% with 2.5 mm vs 52.9% with 3.0 mm (aOR 0.53, 95% CI 0.38-0.75). Among infants weighing 2000 to 2199 g: severe oxygen desaturation, 41% with 3.0 mm versus 56% with 3.5mm (aOR 0.55, 95% CI 0.34-0.89). CONCLUSIONS: For infants weighing 1000 to 1199 g and 2000 to 2199 g, the recommended ETT size was frequently downsized during the procedure, whereas 0.5 mm smaller ETT sizes were associated with fewer adverse events and were rarely upsized.

Is telemedicine suitable for remotely supporting non-tertiary units in providing emergency care to unwell newborns?

Although the majority of term infants will breathe spontaneously at birth, the requirement for advanced resuscitation can be unpredictable, as can the precipitous delivery of an extremely preterm infant in a non-tertiary neonatal unit. Infants born in hospitals without a tertiary neonatal intensive care unit have a higher mortality which is a disparity that has been difficult to resolve.Telemedicine, the use of videoconferencing software to connect those at the scene of a resuscitation to a remote clinician, can allow for real-time two-way communication between a local unit and a tertiary neonatal specialist. It has been present for some time in neonatology to provide secure video messaging with families and its use in neonatal acute care and resuscitation has been growing in recent years.We sought to perform a review of the current evidence available on the use of telemedicine in neonatal resuscitation. Studies demonstrate improved quality of resuscitation, improved adherence to resuscitation guidelines and positive experiences reported by local and tertiary teams. Suitable technology needs to be available to establish a rapid and secure video connection, as does adequate availability of experienced neonatologists to provide remote guidance. Telemedicine is an exciting and emerging tool which is being developed as a standard of care in units which have piloted it.

Alternatives to neonatal intubation.

Opportunities to learn and maintain competence in neonatal intubation have decreased. As many clinicians providing care to the newborn infant are not skilled in intubation, alternative strategies are critical. Most preterm infants breathe spontaneously, and require stabilisation rather than resuscitation at birth. Use of tactile stimulation, deferred cord clamping, and avoidance of hypoxia can help optimise breathing for these infants. Nasal devices appear a promising alternative to the face mask for early provision of respiratory support. In term and near-term infants, supraglottic airways may be the most effective initial approach to resuscitation. Use of supraglottic airways during resuscitation can be taught to a range of providers, and may reduce need for intubation. While face mask ventilation is an important skill, it is challenging to perform effectively. Identification of the best approach to training the use of these devices during neonatal resuscitation remains an important priority.

Videolaryngoscopy in neonatal clinical care.

Endotracheal intubation is a life-saving procedure for many newborns. Historically, it has been achieved by obtaining an airway view through the mouth via direct laryngoscopy. It is a skill that takes time and practice to achieve proficiency. Increasing evidence for the benefit of videolaryngoscopy in adults and the new development of technology has allowed videolaryngoscopy to become a reality in neonatal care. Studies have examined its use as both a technique to improve intubation safety and success, and as a training tool for those learning the skill in this vulnerable population. We present the current evidence for videolaryngoscopy in neonates in different settings where intubation may be required, in addition to exploring the challenges and practicalities of implementing this technique into clinical practice.

Maternal preeclampsia and risk of bronchopulmonary dysplasia in preterm infants.

INTRODUCTION: To better understand whether preeclampsia (PE) increases the risk of bronchopulmonary dysplasia (BPD). RESULTS: Of 753 infants alive at 36 wks, 138 (18.3%) were exposed to PE. BPD was not significantly related to exposure to PE either before (odds ratio (OR) 0.73; 95% confidence interval (CI) 0.50, 1.06) or after adjustment for confounding variables (adjusted OR 1.14; 95% CI 0.71, 1.81). If infants were selected by gestational age alone, there was no association (OR 1.05; 95% CI 0.63, 1.75). In contrast, selecting by birth weight alone, PE was associated with a significant reduction in BPD (OR 0.61, 95% CI 0.41, 0.91). However, this effect disappeared after adjustment for confounding variables. DISCUSSION: Conclusions were unchanged when data from other studies were included in a pooled analysis. PE does not significantly affect the risk of BPD in extremely preterm (EP) or extremely-low-birth-weight (ELBW) subjects. METHODS: We examined data on EP (<28 wks gestation) or ELBW (<1,000 g) infants live born in Victoria, Australia, in three eras: 1991-1992, 1997, and 2005. We compared the incidence of BPD (oxygen requirement at 36 wks' postmenstrual age) in the PE group (infants exposed to PE) with that in the remainder (nonexposed infants). We also contrasted results with comparable reported studies.

Safe emergency neonatal airway management: current challenges and potential approaches.

This review examines the airway adjuncts currently used to acutely manage the neonatal airway. It describes the challenges encountered with facemask ventilation and intubation. Evidence is presented on how to optimise intubation safety and success rates with the use of videolaryngoscopy and attention to the intubation environment. The supraglottic airway (laryngeal mask airway) is emerging as a promising neonatal airway adjunct. It can be used effectively with little training to provide a viable alternative to facemask ventilation and intubation in neonatal resuscitation and be used as an alternative conduit for the administration of surfactant.

Neonatal videolaryngoscopy as a teaching aid: the trainees' perspective.

INTRODUCTION: Neonatal intubation is a challenging skill to acquire. A randomised controlled trial (RCT) found junior trainees had higher intubation success rates if their supervisor shared their airway view on a videolaryngoscope screen compared with intubations where the supervisor could not see the videolaryngoscope screen. The intubations in the trial were supervised by a group of experienced neonatologists who developed an intubation teaching package that aimed to be informative, consistent and supportive. We surveyed the trainees to assess their experiences of the intubation attempts. METHODS: Trainees participating in the RCT completed questionnaires anonymously after each intubation attempt. Questionnaires used 5-point Likert scales and free comment sections. Quantitative analysis was performed using descriptive statistics. In a qualitative analysis, free comments were coded to identify central recurring themes. RESULTS: Two hundred and six questionnaires were completed by 36 trainees. The majority reported that the guidance received during intubation was helpful, the postprocedure feedback was educational and their confidence levels were increased. Trainees appreciated a controlled environment and calm, consistent guidance. They found intubations in the delivery room, those involving unstable infants, large audiences and parental presence more stressful. Responses were positive whether the videolaryngoscope screen was visible or covered, emphasising the importance of consistent guidance. Overall, 16% of intubations were reported as intimidating. CONCLUSION: The shared airway view offered by videolaryngoscopy was well received. In addition, taking measures to control the setting, with standardised guidance and feedback, improved confidence and created a more positive learning experience.

Supraglottic airway devices for administration of surfactant to newborn infants with respiratory distress syndrome: a narrative review.

Surfactant is an effective treatment for respiratory distress syndrome, being particularly important for infants in whom continuous positive airway pressure (CPAP) provides insufficient support. Supraglottic airway devices present an attractive option for surfactant delivery, particularly as an alternative to methods dependent on direct laryngoscopy, a procedural skill that is both difficult to learn and in which to maintain competence. Published studies provide encouraging data that surfactant administration by supraglottic airway device can be performed with a high rate of success and may reduce the need for subsequent intubation compared with either continued CPAP or surfactant administration via endotracheal tube. However, existing randomised controlled trials (RCTs) are heterogeneous in design and include just over 350 infants in total. To date, all RCT evidence has been generated in tertiary units, whereas the greatest potential for benefit from the use of these devices is likely to be in non-tertiary settings. Future research should investigate choice and utility of device in addition to safety and effectiveness of procedure. Importantly, studies conducted in non-tertiary settings should evaluate feasibility, meaningful clinical outcomes and the impact that this approach might have on infants and their families. Supraglottic airway devices may represent a simple and effective mode of surfactant administration that can be widely used by a variety of clinicians. However, further well-designed RCTs are required to determine their role, safety and effectiveness in both tertiary and non-tertiary settings before introduction into routine clinical practice.

Effect of opaque wraps for pulse oximeter sensors: randomised cross-over trial.

BACKGROUND: Evidence is lacking as to whether ambient light or phototherapy light could interfere with pulse oximeter performance. METHODS: In this randomised cross-over trial, we recruited neonates of gestation >24 weeks. Consented infants were randomly assigned to either pulse oximeter sensor with opaque wrap or without opaque wrap. Nellcor and Masimo sensors were applied simultaneously to different feet for 10 min of recording. Infants were crossed over to the other intervention for a further 10 min, totalling 20 min recording per infant. Primary outcome was faster acquisition of data with shielding of pulse oximeter sensor as compared with not shielding. RESULTS: A total of 96 babies were recruited. There was no difference in primary outcome of time taken to display valid data between the two groups (opaque wrap: 12.73±3.1 s vs no opaque wrap: 13.16±3.3 s, p=0.27). There was no difference in any of the secondary outcomes (percentage of valid data points, percentage of time saturation below target, and so on) between the two groups in both pulse oximeters. Masimo sensor readings displayed a higher mean oxygen saturation (mean difference of 2.85, p=0.001) and lower percentage of time saturation below 94% (mean difference of -27.8, p=0.001) than Nellcor in both groups. There was no difference in any of the outcomes in babies receiving phototherapy (n=21). CONCLUSION: In this study, shielding the pulse oximeter sensor from ambient light or phototherapy light did not yield faster data acquisition or better data quality. TRIAL REGISTRATION NUMBER: ISRCTN10302534.

Comparison of conventional and videolaryngoscopy blades in neonates.

Neonatal intubation is an essential but difficult skill to learn. Videolaryngoscopy allows the airway view to be shared by the intubator and supervisor and improves intubation success. Ideally, a videolaryngoscope (VL) should be usable as a conventional laryngoscope (CL). The aims of this report were to describe differences in the shape of currently available CL and VL blades and to compare the direct airway view obtainable on a neonatal manikin with different laryngoscope blades.Three main differences were observed; compared with CL, the VL blades have a reduced vertical height, a curved tip and curved body. The direct airway view obtained by the VL is narrower than that obtained with the CL, although the corresponding view on the VL screen is maintained.Minor adaptation of intubation technique may be required when using a VL. Modifying VL blades to reduce these differences may improve their usefulness as an intubation training tool.