A Pilot Randomized Trial of Heart Rate Monitoring Using Conventional Versus a New Electrocardiogram Algorithm during Neonatal Resuscitation at Birth.

Current guidelines support the use of a cardiac monitor during neonatal resuscitation. Infants born preterm randomized to a novel electrocardiogram algorithm displayed a heart rate sooner than the conventional electrocardiogram algorithm. Although resuscitation outcomes were not different, the availability of an earlier heart rate may benefit neonatal providers during high-risk resuscitations. TRIAL REGISTRATION: ClinicalTrials.govNCT04587934.

Early Cardiac and Cerebral Hemodynamics with Umbilical Cord Milking Compared with Delayed Cord Clamping in Infants Born Preterm.

OBJECTIVE: To evaluate changes in cerebral oxygenation, peripheral arterial oxygenation, respiratory status, and administered fraction of inspired oxygen during the first 10 minutes of life in premature infants receiving umbilical cord milking compared with delayed cord clamping (DCC). STUDY DESIGN: Premature infants born at 230/7 to 276/7 weeks of gestation were randomized to umbilical cord milking or DCC. A near infrared spectroscopy sensor, pulse oximeter, and electrocardiogram electrodes were placed. Pulse rate, cerebral tissue oxygenation, peripheral oxygen saturation, airway pressure, and fraction of inspired oxygen were collected for 10 minutes in the delivery room. Longitudinal models were used to compare effects of umbilical cord milking and DCC. RESULTS: Fifty-six infants had cerebral oximetry and advanced monitoring at birth. There was an increased incidence of severe intraventricular hemorrhage in infants who received umbilical cord milking compared with DCC (P = .0211). Longitudinal models suggested that peripheral oxygen saturation was higher in the umbilical cord milking group in the first 4 minutes (P = .0221) and that mean airway pressures were lower in the umbilical cord milking group after the first 7 minutes (P = .0072). No statistical differences were observed for fraction of inspired oxygen, cerebral tissue oxygenation, or heart rates. CONCLUSIONS: The data suggest that the rapid transfer of blood during umbilical cord milking may facilitate lung expansion with improved pulmonary blood flow, but may also increase cerebral blood flow, resulting in severe intraventricular hemorrhage. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03145142.

Laryngeal Mask Airway for Surfactant Administration in Neonates: A Randomized, Controlled Trial.

OBJECTIVE: To determine if preterm infants with moderate respiratory distress syndrome on continuous positive airway pressure (CPAP) who received surfactant via a laryngeal mask airway (LMA) would have a decreased rate of intubation and mechanical ventilation compared with those on CPAP who did not receive surfactant. STUDY DESIGN: In this prospective, multicenter, randomized controlled trial, 103 premature infants 280/7-356/7 weeks gestation, ≥1250 g and ≤36 hours old on CPAP requiring fraction of inspired oxygen 0.30-0.40 were assigned to receive surfactant administered through an LMA then placed back on CPAP (LMA group) or maintained on CPAP with no surfactant administered (control group). The primary outcome was treatment failure necessitating intubation and mechanical ventilation in the first 7 days of life. RESULTS: Surfactant administration through an LMA (n = 50) significantly decreased the rate of intubation and mechanical ventilation compared with controls (n = 53): 38% vs 64%, respectively, OR 0.30 (95% CI 0.13, 0.70), P = .006, number needed to treat: 4). There were no serious adverse events associated with placement of the LMA or surfactant administration. CONCLUSIONS: In premature neonates with moderate respiratory distress syndrome, surfactant administered through an LMA decreased the rate of intubation and mechanical ventilation. This intervention may have significant impact on clinical care in both high and low resource settings. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01116921.

Effects of endotracheal intubation and surfactant on a 3-channel neonatal electroencephalogram.

OBJECTIVE: To evaluate the effects of surfactant administration on the neonatal brain using 3-channel neonatal electroencephalography (EEG). STUDY DESIGN: A prospective cohort of 30 infants had scalp electrodes placed to record brain waves using 3-channel EEG (Fp1-O1, C3-C4, and Fp2-O2). Sixty-second EEG epochs were collected from a 10-minute medication-free baseline, during premedication for endotracheal intubation, at surfactant administration, and at 10, 20, and 30 minutes after surfactant administration for amplitude comparisons. Oxygen saturation and heart rate were monitored continuously. Blood pressure and transcutaneous carbon dioxide were recorded every 5 minutes. RESULTS: Eighteen of 29 infants (62%) exhibited brain wave suppression on EEG after surfactant administration (P ≤ .008). Four of those 18 infants did not receive premedication. Nine infants exhibited evidence of EEG suppression during endotracheal intubation, all of whom received premedication before intubation. Five infants had EEG suppression during endotracheal suctioning. Oxygen saturation, heart rate, and blood pressure were not independent predictors of brain wave suppression. CONCLUSION: Eighteen of 29 intubated infants (62%) had evidence of brain wave suppression on raw EEG after surfactant administration. Nine patients had evidence of brief EEG suppression with endotracheal intubation alone, a finding not previously reported in neonates. Intubation and surfactant administration have the potential to alter cerebral function in neonates.

Association between early cerebral oxygenation and neurodevelopmental impairment or death in premature infants.

OBJECTIVE: To assess the relationship between cerebral oxygenation in the first 72 h of life and neurodevelopmental impairment (NDI) at 2 years corrected age in former premature infants. STUDY DESIGN: Prospective observational cohort study of 127 infants <32 weeks GA at birth with cerebral oxygenation monitoring using NIRS in the first 72 h of life. RESULTS: Using a threshold cutoff for cerebral hypoxia, infants with NDI or death had increased duration of hypoxia (4 vs 2.3%, p = 0.001), which was more pronounced in the 23-27 week subgroup (7.6 vs 3.2%, p < 0.001). Individual generalized estimating equations to adjust for repeated measures were modeled in this subgroup for the physiologic parameters including StO2. StO2 < 67% was a predictor for death or NDI (OR 2.75, 95% CI 1.006, 7.5132, p = 0.049). CONCLUSION: An increased duration of cerebral hypoxia is associated with NDI or death in infants born <32 weeks GA.

Waived Consent in Perinatal/Neonatal Research-When Is It Appropriate?

Informed consent is a process ensuring that subjects enrolled in research are appropriately informed of the risks and benefits. While this process is well-defined when it is possible and practical to obtain consent prior to the research intervention, it can be less clear in cases of deferred or waived consent. Defining minimal risk, such as when research is attempting to determine which of two currently practiced interventions is safest and/or most effective, is critical to moving forward in establishing appropriate care in newborns. For perinatal/neonatal research the challenge lies between the ethical justification for approaching women in labor or under medication vs. the scientific integrity of excluding a number of subjects that may potentially benefit the most from an intervention. Researchers must work with their IRBs as well as families who have participated in trials to determine the most appropriate method for obtaining informed consent from expectant parents. Clinical researchers and IRBs ultimately need to find a middle ground for the appropriate use of deferred or waived consent.

Circulatory emergencies in the delivery room.

The transition from fetal to neonatal life is a dramatic and complex process involving extensive physiologic changes, which are most obvious at the time of birth. Individuals who care for newly born infants must monitor the progress of the transition and be prepared to intervene when necessary. In the majority of births, this transition occurs without a requirement for any significant assistance. If newborns require assistance, the majority of the time respiratory support is all that is required. In some instances, however, there are circulatory emergencies that need to be rapidly identified or there may be dire consequences including death in the delivery room. This chapter will review various pathologies that are circulatory emergencies, and discuss how to assess them. We will also review new technologies which may help providers better understand the circulatory status or hemodynamic changes in the delivery room including heart rate, cardiac output, cerebral oxygenation and echocardiography.

Placental Transfusion for Asphyxiated Infants.

The current recommendation for umbilical cord management of non-vigorous infants (limp, pale, and not breathing) who need resuscitation at birth is to immediately clamp the umbilical cord. This recommendation is due in part to insufficient evidence for delayed cord clamping (DCC) or umbilical cord milking (UCM). These methods may provide a neuroprotective mechanism that also facilitates cardiovascular transition for non-vigorous infants at birth.

Incidence of Hypocapnia, Hypercapnia, and Acidosis and the Associated Risk of Adverse Events in Preterm Neonates.

BACKGROUND: Permissive hypercapnia is a lung-protection strategy. We sought to review our current clinical practice for the range of permissive hypercapnia and identify the relationship between PaCO2 and pH and adverse outcomes. METHODS: A secondary analysis of a delayed cord-clamping clinical trial was performed on all arterial blood gas tests in the first 72 h in infants < 32 weeks gestational age. All arterial blood gas values were categorized into a clinical range to determine the percent likelihood of occurring in the total sample. The univariate and multivariate relationships of severe adverse events and the time-weighted PaCO2 , fluctuation of PaCO2 , maximal and minimal PaCO2 , base excess, and pH were assessed. RESULTS: 147 infants with birthweight of 1,206 ± 395 g and gestational age of 28 ± 2 weeks were included. Of the 1,316 total samples, < 2% had hypocapnia (PaCO2 <30 mm Hg), 47% were normocapnic (PaCO2 35-45 mm Hg), 26.5% had mild hypercapnia (PaCO2 45-55 mm Hg), 13% had moderate hypercapnia (PaCO2 55-65 mm Hg), and 6.5% had severe hypercapnia (PaCO2 ≥ 65 mm Hg). There were no adverse events associated with hypocapnia. Subjects with death/severe intraventricular hemorrhage had a higher mean PaCO2 of 52.3 versus 44.7 (odds ratio [OR] 1.16, 95% CI 1.04-1.29, P = .006), higher variability of PaCO2 with a standard deviation of 12.6 versus 7.8 (OR 1.15, 95% CI 1.03-1.27, P = .01), and a lower minimum pH of 7.03 versus 7.23 (OR 0, 95% CI 0-0.06, P = .003). There was no significant difference in any variables in subjects who developed other adverse events. CONCLUSION: The routine targeting of higher than normal PaCO2 goals may lead to a low incidence of hypocapnia and associated adverse events. Hypercapnia is common, and moderate hypercapnia may increase the risk of neurologic injury and provide little pulmonary benefit.

Waiver of Consent in a Trial Intervention Occurring at Birth-How Do Parents Feel?

BACKGROUND: We have previously demonstrated that it is difficult to obtain a representative subject sample when conducting a randomized controlled trial (RCT) at or near the time of birth and obtaining antenatal consent. Waiver of consent has been used in neonatal trials, but parents' reactions to being enrolled in these trials have never been reported. METHODS: The parents enrolled in a RCT involving a waiver of consent with a post-delivery discussion were asked to take part in a brief survey. The survey questions included the timing of when parents were informed about the study, and how they felt about their infants being included in the study. RESULTS: Forty-nine parents completed the online survey. Sixty-nine percent (n = 34) remembered a physician discussing their premature baby with them prior to delivery. Thirty-four percent (17) indicated the physician had discussed participation in the study prior to delivery. Sixty-nine percent (34) indicated that they had a positive or strongly positive feeling about the studies impact on their baby's health. CONCLUSION: Our study demonstrates that the majority of responding parents of infants who have actually participated in a RCT with a waiver of consent process had a positive response, a minority had a neutral response, and none had a slightly negative or highly negative response to participation in the study.

Resistance of Colorimetric Carbon Dioxide Detectors Commonly Utilized in Neonates.

BACKGROUND: Colorimetric end-tidal carbon dioxide (ETCO2) detectors can identify airway obstruction during noninvasive ventilation and successful intubation during newborn resuscitation. The resistance of these devices is not well described, and the information provided by manufacturers is incomplete. METHODS: We compared the resistance of 3 colorimetric ETCO2 detectors (Neo-StatCO2, Pedi-Cap, and Mini StatCO2,) and 2 mainstream capnograph sensors (EMMA infant airway adapter 17449 and neonatal/infant airway adapter YG-213T). Endotracheal tubes, 2.5-4.0-mm inner diameter (Portex) were measured as a reference range. A differential pressure transducer was placed between the device and a T-piece resuscitator. The other side of the device was open to air. Resistance to flow was tested at 1-10 L/min. Resistance was calculated as the change in pressure over change in flow and expressed as cm H2O/L/s. RESULTS: There was a significantly higher mean resistance across all flows tested for the Neo-StatCO2 compared with the other ETCO2 devices (P < .001). There was a 6-fold difference between the least and most resistive colorimetric detectors. At the commonly utilized flow of 10 L/min, the resistance of the Neo-StatCO2 was 61.1 cm H2O/L/s, comparable with that of a 3.0 endotracheal tube, which we measured at 62.7 cm H2O/L/s. The resistance values of the Pedi-Cap and Mini StatCO2 were 9.9 and 8.4 cm H2O/L/s, respectively. Those of the EMMA and YG-213T were 7.1 and 2.6 cm H2O/L/s, respectively. CONCLUSIONS: We found significant differences in resistance between devices used to detect ETCO2 during resuscitation of premature infants. Future trials are needed to determine the effects of this resistance on work of breathing, particularly on very premature newborns receiving mask CPAP.

Unintentional variation in positive end expiratory pressure during resuscitation with a T-piece resuscitator.

INTRODUCTION: The ability of T-piece resuscitators to deliver consistent peak inspiratory pressure (PIP) and positive end expiratory pressure (PEEP) during real and simulated neonatal resuscitation has been well described. The Neopuff (Fisher & Paykel Healthcare, Auckland, New Zealand) has been the device used for nearly all of these comparisons. METHODS: All high risk resuscitations were carried out in our dedicated resuscitation room, and were recorded on video tape for quality assurance purposes.(1) In addition to the audio and video recording, physiologic signals and resuscitation parameters, including oxygen saturation, pulse rate, airway pressure, FiO(2), and others signals as appropriate were also captured. These recordings were reviewed on a biweekly basis as part of a continuing quality review process. Resuscitations were graded for standard of care and the resuscitation checklist was reviewed to determine if the team had any unresolved issues that needed to be addressed. RESULTS: In the year between April of 2009 and March 2010, a period when we fully reviewed approximately 120 videos, we recognized visually obvious PEEP changes on 8 different occasions in ELBW infants. Our target PEEP was 5 cm H20. We observed rapid changes in the PEEP to as high as 15 cm H20 during resuscitation. CONCLUSION: Based on our single-center experience, a T-piece resuscitation device which has the adjustment for the PEEP level and the orifice which is occluded to deliver a breath in the same location has the potential to cause an inadvertent and potentially toxic increase of PEEP which might not be noticed by the operator.

Delivery room intervention: improving the outcome.

The authors have conducted video review of neonatal resuscitations since 1999. Over this 10-year period 3 phases of our experience have been recognized. Our early reviews helped us recognize what we were doing in the delivery room, an area that had been ignored in improved intervention. It was noted that on many occasions multiple people were trying to accomplish the same task, that bag and mask ventilation was almost exclusively the purview of the respiratory therapists and was not performed well by others, and that infants with low birth weight were often hypothermic on admission. After determining what was being done and how well it was being done, we moved on to how to do it better. This period included making environmental changes by warming the room, the use of occlusive wrap, determining the effectiveness of bag and mask ventilation with colorimetric CO(2) detectors, and the introduction of crew resource management to develop consistent and effective communication. The third and current phase of our experience is to determine how these interventions affect delivery room and potentially later outcomes. Well-designed clinical trials are still needed to further establish the most optimal resuscitation interventions.

Antenatal consent in the SUPPORT trial: challenges, costs, and representative enrollment.

OBJECTIVES: The purposes of this study were to quantify the time and effort involved in obtaining prenatal consent for the Neonatal Research Network Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial (SUPPORT) and to determine whether the enrolled infants were representative of the eligible population. METHODS: Eligible subjects were likely to deliver in the SUPPORT gestational age window (24-27(6/7)] weeks). Data included who approached the subjects for consent, how often they approached, the duration of each contact, whether consent was obtained, and whether subjects were enrolled in the trial. Eligible, nonenrolled infants entered into the Neonatal Research Network Generic Database throughout the period of SUPPORT enrollment were compared with enrolled infants. RESULTS: A total of 2826 women were identified at 18 sites, 2228 were approached for consent, and 1219 (54.7%) agreed. For 76.9% of those approached, <3 visits (mean: 2.0 +/- 1.2 visits) were required to complete the consent process. Of the 659 infants with consent who were delivered within the study window, 611 were enrolled. Mothers who received a neonatal consultation were more likely to give consent (P < .001). The proportion of infants not exposed to steroids was significantly greater in the nonapproached group than in the approached group (20.0% vs 3.4%; P < .0001). CONCLUSION: In a trial that involved preterm infants and required prenatal consent, >5 women were identified as being likely to deliver in the SUPPORT gestational age window for each 1 who delivered an enrolled infant.

Premedication for nonemergent neonatal intubations: a randomized, controlled trial comparing atropine and fentanyl to atropine, fentanyl, and mivacurium.

OBJECTIVE: The purpose of this work was to investigate whether using a muscle relaxant would improve intubation conditions in infants, thereby decreasing the incidence and duration of hypoxia and time and number of attempts needed to successfully complete the intubation procedure. PATIENTS/METHODS: This was a prospective, randomized, controlled, 2-center trial. Infants requiring nonemergent intubation were randomly assigned to receive atropine and fentanyl or atropine, fentanyl, and mivacurium before intubation. Incidence and duration of hypoxia were determined at oxygen saturation thresholds of < or = 85%, < or = 75%, < or = 60%, and < or = 40%. Videotape was reviewed to determine the time and number of intubation attempts and duration of action of mivacurium. RESULTS: Analysis of 41 infants showed that incidence of oxygen saturation < or = 60% of any duration was significantly less in the mivacurium group (55% vs 24%). The incidence of saturation level of any duration < or = 85%, 75%, and 40%; cumulative time > or = 30 seconds; and time below the thresholds were not significantly different. Total procedure time (472 vs 144 seconds) and total laryngoscope time (148 vs 61 seconds) were shorter in the mivacurium group. Successful intubation was achieved in < or = 2 attempts significantly more often in the mivacurium group (35% vs 71%). CONCLUSIONS: Premedication with atropine, fentanyl, and mivacurium compared with atropine and fentanyl without a muscle relaxant decreases the time and number of attempts needed to successfully intubate while significantly reducing the incidence of severe desaturation. Premedication including a short-acting muscle relaxant should be considered for all nonemergent intubations in the NICU.

Neonatal resuscitation: raising the bar.

PURPOSE OF REVIEW: To provide an overview of neonatal resuscitation practices with an emphasis on interventions that are not currently accepted or adapted into existing resuscitation guidelines. RECENT FINDINGS: Current resuscitation guidelines do not contain specific guidelines for the approach to the extremely low birth weight infant. The differences in environment and management between the neonatal ICU and delivery room are striking and are magnified in the resuscitation of extremely low birth weight infants for whom maintenance of a neutral thermal environment is essential. The use of a polyethylene wrap applied at delivery has been shown to reduce the occurrence of hypothermia and decrease mortality. There is substantial evidence that term and near-term newborn infants can be effectively resuscitated with room air, and recent follow-up studies have demonstrated that this approach is not associated with increased significant differences in neurologic handicap, somatic growth, or developmental milestones when compared with the use of 100% oxygen. The safety and potential benefits of this approach require prospective evaluation in the premature and especially extremely low birth weight infant. There is preexisting evidence that demonstrates that the use of prolonged inflations and t-piece resuscitators may be advantageous during resuscitation, but not all guidelines support these interventions. Although regulated continuous positive airway pressure, pulse oximeters, and blenders are routinely used once an infant is admitted to the neonatal ICU, none of these interventions is recommended in the delivery area. Although prospective studies have demonstrated that the use of colorimetric CO2 detectors significantly decreases the time to recognize misplaced endotracheal tubes placed during resuscitation, their use is not required by current guidelines. The duration of an intubation attempt during resuscitation had never been prospectively evaluated, and our recent findings suggest that a limit of 30 seconds is well tolerated and provides adequate time for a successful attempt. SUMMARY: There is significant potential for improvement in current resuscitation environments and interventions that will only be realized through further prospective research.