Chest compressions superimposed with sustained inflation during neonatal cardiopulmonary resuscitation: are we ready for a clinical trial?

Neonates requiring cardiopulmonary resuscitation (CPR) are at risk of mortality and neurodevelopmental injury. Poor outcomes following the need for chest compressions (CCs) in the delivery room prompt the critical need for improvements in resuscitation strategies. This article explores a technique of CPR which involves CCs with sustained inflation (CC+SI). Unique features of CC+SI include (1) improved tidal volume delivery, (2) passive ventilation during compressions, (3) uninterrupted compressions and (4) improved stability of cerebral blood flow during resuscitation. CC+SI has been shown in animal studies to have improved time to return of spontaneous circulation and reduced mortality without significant increase in markers of inflammation and injury in the lung and brain, compared with standard CPR. The mechanics of CCs, rate of compressions, ventilation strategies and compression-to-ventilation ratios are detailed here. A large randomised controlled trial comparing CC+SI versus the current 3:1 compression-to-ventilation ratio is needed, given the growing evidence of its potential benefits.

Early Echocardiographic Predictors of Eventual Need for Patent Ductus Arteriosus Treatment: A Retrospective Study.

OBJECTIVE: Hemodynamically significant patent ductus arteriosus (hsPDA) in preterm neonates is associated with end-organ injury including intraventricular hemorrhage. Early treatment may reduce morbidities but may result in overtreatment. This study aimed to examine the association between commonly obtained echocardiographic markers within the first 12 hours of life and eventual treatment of an hsPDA. STUDY DESIGN: Patients with <32 weeks' gestational age had blinded echocardiograms done within the first 12 hours of life as part of research protocols. Subsequent treatment of the patent ductus arteriosus (PDA) was determined by the clinical team independent of echocardiogram results. t-tests and chi-square tests were done for continuous data and categorical outcomes. A receiver operating curve was created to optimize cutoff values. RESULTS: Among 199 neonates studied (mean time of echocardiogram 6.7 h after birth), those needing PDA treatment had higher left ventricular output (LVO), right ventricular output (RVO), and superior vena cava (SVC) flow (p-values 0.007, 0.044, and 0.012, respectively). Cutoffs for predicting PDA treatment were LVO > 204 mL/kg/min (63% sensitivity, 66% specificity), RVO > 221 mL/kg/min or SVC flow > 99 mL/kg/min (sensitivities 70 and 43%, specificities 48 and 73%, respectively). CONCLUSION: Preterm neonates with higher markers of cardiac output in the first 12 hours of birth later required PDA treatment. These data are the first to use standard cardiac output measures in the first 12 hours of life to predict the need for future PDA treatment. Further prospective studies will need to be performed to corroborate these associations between echocardiographic markers and clinical outcomes/morbidities. KEY POINTS: · Early diagnosis of hsPDA may prevent severe morbidity and death.. · There are echocardiographic markers beyond duct size and flow direction that may aid early diagnosis.. · Cardiac output markers within the first 12 hours of life may predict need for treatment of hsPDA..

Application of desirability of outcome ranking to the milking in non-vigorous infants trial.

OBJECTIVES: Neonatal trials have traditionally used binary composite short-term (such as death or bronchopulmonary dysplasia) or longer-term (such as death or severe neurodevelopmental impairment) outcomes. We applied the Desirability Of Outcome Ranking (DOOR) method to rank the overall patient outcome by best (no morbidities) to worst (death). STUDY DESIGN: Using a completed large multicenter trial (Milking In Non-Vigorous Infants [MINVI]) of umbilical cord milking (UCM) vs. early cord clamping (ECC), we applied the DOOR methodology to neonatal outcomes. Six outcomes were chosen and ranked: no interventions or NICU admission (most desirable); received initial cardiorespiratory support at birth; neonatal intensive care unit (NICU) admission for predefined criteria; mild hypoxic-ischemic encephalopathy (HIE); moderate to severe HIE; and death (least desirable). RESULTS: 1524 non-vigorous newborns born between 35 and 42 weeks' gestation had data for analysis. The DOOR distribution was different between the UCM and ECC arms, with a significantly greater probability (55.8 % [95 % CI 53.1-58.5 %; p < 0.0001]) of a randomly selected neonate having a more desirable outcome if they were in the UCM arm. DOOR probabilities of averting individual adverse outcomes such as NICU admission for predefined criteria (52.8 %; 95%CI 50.5-55.1 %) and cardiorespiratory support (54.0 %; 95%CI 51.6-56.4 %) were significantly higher among those in the UCM group. CONCLUSION: DOOR provides an overall assessment of the benefits and harms with greater insight than typical binary composite measures to clinicians and parents when evaluating an intervention. Future neonatal trials should consider the a priori use of the DOOR methodology to evaluate trial outcomes.

Parental perspectives on a trial using waived informed consent at birth.

OBJECTIVES: To determine parental perspectives in a trial with waived consent. STUDY DESIGN: Anonymous survey of birth parents with term infants who were randomized using a waiver of consent, administered after infant discharge. RESULTS: 121 (11%) survey responses were collected. Of the 121 responding parents 111 (92%) reported that this form of consent was acceptable and 116 (96%) reported feeling comfortable having another child participate in a similar study. 110 (91%) respondents reported that they both understood the information provided in the consent process and had enough time to consider participation. Four percent had a negative opinion on the study's effect on their child's health. CONCLUSIONS: Most responding parents reported both acceptability of this study design in the neonatal period and that the study had a positive effect on their child's health. Future work should investigate additional ways to involve parents and elicit feedback on varied methods of pediatric consent.

Umbilical Cord Milking Versus Delayed Cord Clamping in Infants 28 to 32 Weeks: A Randomized Trial.

OBJECTIVES: To determine whether rate of severe intraventricular hemorrhage (IVH) or death among preterm infants receiving placental transfusion with UCM is noninferior to delayed cord clamping (DCC). METHODS: Noninferiority randomized controlled trial comparing UCM versus DCC in preterm infants born 28 to 32 weeks recruited between June 2017 through September 2022 from 19 university and private medical centers in 4 countries. The primary outcome was Grade III/IV IVH or death evaluated at a 1% noninferiority margin. RESULTS: Among 1019 infants (UCM n = 511 and DCC n = 508), all completed the trial from birth through initial hospitalization (mean gestational age 31 weeks, 44% female). For the primary outcome, 7 of 511 (1.4%) infants randomized to UCM developed severe IVH or died compared to 7 of 508 (1.4%) infants randomized to DCC (rate difference 0.01%, 95% confidence interval: (-1.4% to 1.4%), P = .99). CONCLUSIONS: In this randomized controlled trial of UCM versus DCC among preterm infants born between 28 and 32 weeks' gestation, there was no difference in the rates of severe IVH or death. UCM may be a safe alternative to DCC in premature infants born at 28 to 32 weeks who require resuscitation.

Parental Perspectives on a Trial Using Waived Informed Consent at Birth.

Objectives: To determine parental perspectives in a trial with waived consent. Study Design: Biological parents of non-vigorous term infants randomized using a waiver of consent for a delivery room intervention completed an anonymous survey after discharge. Results: 121 survey responses were collected. Most responding parents reported that this form of consent was acceptable (92%) and that they would feel comfortable having another child participate in a similar study (96%). The majority (> 90%) also reported that the information provided after randomization was clear to understand future data collection procedures. Four percent had a negative opinion on the study's effect on their child's health. Conclusions: The majority of responding parents reported both acceptability of this study design in the neonatal period and that the study had a positive effect on their child's health. Future work should investigate additional ways to involve parents and elicit feedback on varied methods of pediatric consent.

Thermoregulation-Focused Implementation of Delayed Cord Clamping among <34 Weeks' Gestational Age Neonates.

OBJECTIVE: Delayed cord clamping (DCC) is recommended for all neonates; however, adapting such practice can be slow or unsustainable, especially among preterm neonates. During DCC neonates are exposed to a cool environment, raising concerns for neonatal hypothermia. Moderate hypothermia may induce morbidities that counteract the potential benefits of DCC. A quality improvement project on a thermoregulation-focused DCC protocol was implemented for neonates less than 34 weeks' gestational age (GA). The aim was to increase the compliance rate of DCC while maintaining normothermia. STUDY DESIGN: The DCC protocol was implemented on October 1, 2020 in a large Level III neonatal intensive care unit. The thermoregulation measures included increasing delivery room temperature and using heat conservation supplies (sterile polyethylene suit, warm towels, and thermal pads). Baseline characteristics, the compliance rate of DCC, and admission temperatures were compared 4 months' preimplementation and 26 months' postimplementation RESULTS: The rate of DCC increased from 20% (11/54) in preimplementation to 57% (240/425) in postimplementation (p < 0.001). The balancing measure of admission normothermia remained unchanged. In a postimplementation subgroup analysis, the DCC cohort had less tendency to experience admission moderate hypothermia (<36°C; 9.2 vs. 14.1%, p = 0.11). The DCC cohort had more favorable secondary outcomes including higher admission hematocrit, less blood transfusions, less intraventricular hemorrhage, and lower mortality. Improving the process measure of accurate documentation could help to identify implementation barriers. CONCLUSION: Performing DCC in preterm neonates was feasible and beneficial without increasing admission hypothermia. KEY POINTS: · Thermoregulation-focused DCC protocol was implemented to increase DCC while maintaining normothermia.. · DCC rate increased from 20 to 57% while admission normothermia rate remained the same.. · DCC practice on preterm neonates is safe and feasible while maintaining normothermia..

Optimizing transition: Providing oxygen during intact cord resuscitation.

Delayed clamping and cutting of the umbilical cord at birth is standard practice for management for all newborns. Preterm infants may additionally benefit from a combination of ventilation and oxygen provision during intact cord resuscitation. This review highlights both the potential benefits of such a combined approach and the need for further rigorous studies, including randomized controlled trials, of delivery room management in this population.

A Narrative Review of the Rationale for Conducting Neonatal Emergency Studies with a Waived or Deferred Consent Approach.

Emergency research studies are high-stakes studies that are usually performed on the sickest patients, where many patients or guardians have no opportunity to provide full informed consent prior to participation. Many emergency studies self-select healthier patients who can be informed ahead of time about the study process. Unfortunately, results from such participants may not be informative for the future care of sicker patients. This inevitably creates waste and perpetuates uninformed care and continued harm to future patients. The waiver or deferred consent process is an alternative model that may be used to enroll sick patients who are unable to give prospective consent to participate in a study. However, this process generates vastly different stakeholder views which have the potential to create irreversible impediments to research and knowledge. In studies involving newborn infants, consent must be sought from a parent or guardian, and this adds another layer of complexity to already fraught situations if the infant is very sick. In this manuscript, we discuss reasons why consent waiver or deferred consent processes are vital for some types of neonatal research, especially those occurring at and around the time of birth. We provide a framework for conducting neonatal emergency research under consent waiver that will ensure the patient's best interests without compromising ethical, beneficial, and informative knowledge acquisition to improve the future care of sick newborn infants.

Curriculum and assessment tool for less invasive surfactant administration: an international Delphi consensus study.

BACKGROUND: Training and assessment of operator competence for the less invasive surfactant administration (LISA) procedure vary. This study aimed to obtain international expert consensus on LISA training (LISA curriculum (LISA-CUR)) and assessment (LISA assessment tool (LISA-AT)). METHODS: From February to July 2022, an international three-round Delphi process gathered opinions from LISA experts (researchers, curriculum developers, and clinical educators) on a list of items to be included in a LISA-CUR and LISA-AT (Round 1). The experts rated the importance of each item (Round 2). Items supported by more than 80% consensus were included. All experts were asked to approve or reject the final LISA-CUR and LISA-AT (Round 3). RESULTS: A total of 153 experts from 14 countries participated in Round 1, and the response rate for Rounds 2 and 3 was >80%. Round 1 identified 44 items for LISA-CUR and 22 for LISA-AT. Round 2 excluded 15 items for the LISA-CUR and 7 items for the LISA-AT. Round 3 resulted in a strong consensus (99-100%) for the final 29 items for the LISA-CUR and 15 items for the LISA-AT. CONCLUSIONS: This Delphi process established an international consensus on a training curriculum and content evidence for the assessment of LISA competence. IMPACT: This international consensus-based expert statement provides content on a curriculum for the less invasive surfactant administration procedure (LISA-CUR) that may be partnered with existing evidence-based strategies to optimize and standardize LISA training in the future. This international consensus-based expert statement also provides content on an assessment tool for the LISA procedure (LISA-AT) that can help to evaluate competence in LISA operators. The proposed LISA-AT enables standardized, continuous feedback and assessment until achieving proficiency.

Umbilical cord milking-benefits and risks.

The most common methods for providing additional placental blood to a newborn are delayed cord clamping (DCC) and umbilical cord milking (UCM). However, DCC carries the potential risk of hypothermia due to extended exposure to the cold environment in the operating room or delivery room, as well as a delay in performing resuscitation. As an alternative, umbilical cord milking (UCM) and delayed cord clamping with resuscitation (DCC-R) have been studied, as they allow for immediate resuscitation after birth. Given the relative ease of performing UCM compared to DCC-R, UCM is being strongly considered as a practical option in non-vigorous term and near-term neonates, as well as preterm neonates requiring immediate respiratory support. However, the safety profile of UCM, particularly in premature newborns, remains a concern. This review will highlight the currently known benefits and risks of umbilical cord milking and explore ongoing studies.

Characteristics and Outcomes in Preterm Infants with Extubation Failure in the First Week of Life.

OBJECTIVE: This study aimed to evaluate characteristics and outcomes in preterm infants with extubation failures in their first week of life. STUDY DESIGN: Retrospective chart review of infants born between 24 and 27 weeks' gestational age at the Sharp Mary Birch Hospital for Women and Newborns between January 2014 and December 2020 who had an extubation attempt within the first 7 days of life. Infants that were successfully extubated were compared with those who required reintubation in the first 7 days. Maternal and neonatal outcome measures were analyzed. RESULTS: A total of 215 extremely preterm infants had an extubation attempt in the first 7 days of life. Forty-six infants (21.4%) failed extubation and were reintubated within the first 7 days. Infants who failed extubation had a lower pH (p < 0.01), increased base deficit (p < 0.01), and more surfactant doses prior to first extubation (p < 0.01). Birth weight, Apgar scores, antenatal steroid doses, and maternal risk factors such as preeclampsia, chorioamnionitis, and duration of ruptured membranes were not different between success and failure groups. Rates of moderate to large patent ductus arteriosus (p < 0.01), severe intraventricular hemorrhage (p < 0.01), posthemorrhagic hydrocephalus (p < 0.05), periventricular leukomalacia (p < 0.01), and retinopathy of prematurity stage 3 or greater (p < 0.05) were higher in the failure group. CONCLUSION: In this cohort of extremely preterm infants that failed extubation in the first week of life, there were as increased risk of multiple morbidities. Base deficit, pH, and number of surfactant doses prior to first extubation may be useful tools in predicting which infants are likely to have early extubation success, but this needs prospective study. KEY POINTS: · Predicting extubation readiness in preterm infants remains challenging.. · Extubation failure is associated with multiple neonatal morbidities.. · Infant clinical characteristics may help predict extubation failure..

Hemodynamic Changes with Umbilical Cord Milking in Nonvigorous Newborns: A Randomized Cluster Cross-over Trial.

OBJECTIVE: To assess the hemodynamic safety and efficacy of umbilical cord milking (UCM) compared with early cord clamping (ECC) in nonvigorous newborn infants enrolled in a large multicenter randomized cluster-crossover trial. STUDY DESIGN: Two hundred twenty-seven nonvigorous term or near-term infants who were enrolled in the parent UCM vs ECC trial consented for this substudy. An echocardiogram was performed at 12 ± 6 hours of age by ultrasound technicians blinded to randomization. The primary outcome was left ventricular output (LVO). Prespecified secondary outcomes included measured superior vena cava (SVC) flow, right ventricular output (RVO), peak systolic strain, and peak systolic velocity by tissue Doppler examination of the RV lateral wall and the interventricular septum. RESULTS: Nonvigorous infants receiving UCM had increased hemodynamic echocardiographic parameters as measured by higher LVO (225 ± 64 vs 187 ± 52 mL/kg/min; P < .001), RVO (284 ± 88 vs 222 ± 96 mL/kg/min; P < .001), and SVC flow (100 ± 36 vs 86 ± 40 mL/kg/min; P < .001) compared with the ECC group. Peak systolic strain was lower (-17 ± 3 vs -22 ± 3%; P < .001), but there was no difference in peak tissue Doppler flow (0.06 m/s [IQR, 0.05-0.07 m/s] vs 0.06 m/s [IQR, 0.05-0.08 m/s]). CONCLUSIONS: UCM increased cardiac output (as measured by LVO) compared with ECC in nonvigorous newborns. Overall increases in measures of cerebral and pulmonary blood flow (as measured by SVC and RVO flow, respectively) may explain improved outcomes associated with UCM (less cardiorespiratory support at birth and fewer cases of moderate-to-severe hypoxic ischemic encephalopathy) among nonvigorous newborn infants.

Cardiac and cerebral hemodynamics with umbilical cord milking compared with early cord clamping: A randomized cluster crossover trial.

OBJECTIVE: A large, randomized cluster cross-over trial (N = 1730) comparing intact umbilical cord milking (UCM) to early cord clamping (ECC) in non-vigorous near-term/term newborns demonstrated a reduction in cardiorespiratory interventions at birth and less moderate to severe hypoxic ischemic encephalopathy. We evaluated changes in cerebral tissue oxygenation (StO2), pulse oximetry (SpO2), pulse rate and fraction of inspired oxygen (FiO2) during the first 10 min of life in a subset of infants enrolled in the parent trial. STUDY DESIGN: Infants enrolled in the Milking in Non-Vigorous Infants trial that had StO2 monitoring at birth were included in the sub-study conducted at 3 hospitals the US and Canada. A near-infrared spectroscopy sensor, pulse oximeter and electrocardiogram electrodes were placed. Pulse rate, StO2, SpO2, and FiO2 were collected for the first 10 min after birth. Longitudinal models were used to compare effects of UCM and ECC. RESULTS: Thirty-four infants had StO2 data. Fifteen of these infants received UCM and 19 had ECC. Infants receiving UCM had similar heart rates, SpO2, and StO2 values, but were exposed to less FiO2 over the first 10 min of life than infants with ECC (0.26 ± 0.12 vs. 0.81 ± 0.05 at 10 min). CONCLUSION: Non-vigorous term/near term infants who received UCM at birth required lower FiO2 after delivery when compared to infants who umbilical cords were clamped soon after birth while achieving similar peripheral and cerebral oxygenation. Cord milking may be a potential option for placental transfusion in non-vigorous near term/term infants when delayed cord clamping cannot be performed.

Point-of-care ultrasound (POCUS) protocol for systematic assessment of the crashing neonate-expert consensus statement of the international crashing neonate working group.

Sudden unexpected clinical deterioration or cardiorespiratory instability is common in neonates and is often referred as a "crashing" neonate. The established resuscitation guidelines provide an excellent framework to stabilize and evaluate these infants, but it is primarily based upon clinical assessment only. However, clinical assessment in sick neonates is limited in identifying underlying pathophysiology. The Crashing Neonate Protocol (CNP), utilizing point-of-care ultrasound (POCUS), is specifically designed for use in neonatal emergencies. It can be applied both in term and pre-term neonates in the neonatal intensive care unit (NICU). The proposed protocol involves a stepwise systematic assessment with basic ultrasound views which can be easily learnt and reproduced with focused structured training on the use of portable ultrasonography (similar to the FAST and BLUE protocols in adult clinical practice). We conducted a literature review of the evidence-based use of POCUS in neonatal practice. We then applied stepwise voting process with a modified DELPHI strategy (electronic voting) utilizing an international expert group to prioritize recommendations. We also conducted an international survey among a group of neonatologists practicing POCUS. The lead expert authors identified a specific list of recommendations to be included in the proposed CNP. This protocol involves pre-defined steps focused on identifying the underlying etiology of clinical instability and assessing the response to intervention.Conclusion: To conclude, the newly proposed POCUS-based CNP should be used as an adjunct to the current recommendations for neonatal resuscitation and not replace them, especially in infants unresponsive to standard resuscitation steps, or where the underlying cause of deterioration remains unclear. What is known? • Point-of-care ultrasound (POCUS) is helpful in evaluation of the underlying pathophysiologic mechanisms in sick infants. What is new? • The Crashing Neonate Protocol (CNP) is proposed as an adjunct to the current recommendations for neonatal resuscitation, with pre-defined steps focused on gaining information regarding the underlying pathophysiology in unexplained "crashing" neonates. • The proposed CNP can help in targeting specific and early therapy based upon the underlying pathophysiology, and it allows assessment of the response to intervention(s) in a timely fashion.