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.

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.

Delayed Cord Clamping in Newborns Born at Term at Risk for Resuscitation: A Feasibility Randomized Clinical Trial.

Infants may benefit if resuscitation could be provided with an intact umbilical cord. Infants identified at risk for resuscitation were randomized to 1- or 5-minute cord clamping. The 5-minute group had greater cerebral oxygenation and blood pressure. Studies are needed to determine whether this translates into improved outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02827409.

Noninvasive inhaled nitric oxide does not prevent bronchopulmonary dysplasia in premature newborns.

OBJECTIVE: To assess the efficacy and safety of early, noninvasive inhaled nitric oxide (iNO) therapy in premature newborns who do not require mechanical ventilation. STUDY DESIGN: We performed a multicenter randomized trial including 124 premature newborns who required noninvasive supplemental oxygen within the first 72 hours after birth. Newborns were stratified into 3 different groups by birth weight (500-749, 750-999, 1000-1250 g) prior to randomization to iNO (10 ppm) or placebo gas (controls) until 30 weeks postmenstrual age. The primary outcome was a composite of death or bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age. Secondary outcomes included the need for and duration of mechanical ventilation, severity of BPD, and safety outcomes. RESULTS: There was no difference in the incidence of death or BPD in the iNO and placebo groups (42% vs 40%, P = .86, relative risk = 1.06, 0.7-1.6). BPD severity was not different between the treatment groups. There were no differences between the groups in the need for mechanical ventilation (22% vs 23%; P = .89), duration of mechanical ventilation (9.7 vs 8.4 days; P = .27), or safety outcomes including severe intracranial hemorrhage (3.4% vs 6.2%, P = .68). CONCLUSIONS: We found that iNO delivered noninvasively to premature infants who have not progressed to early respiratory failure is a safe treatment, but does not decrease the incidence or severity of BPD, reduce the need for mechanical ventilation, or alter the clinical course.

Respiratory outcomes of the surfactant positive pressure and oximetry randomized trial (SUPPORT).

OBJECTIVE: To explore the early childhood pulmonary outcomes of infants who participated in the National Institute of Child Health and Human Development's Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial (SUPPORT), using a factorial design that randomized extremely preterm infants to lower vs higher oxygen saturation targets and delivery room continuous positive airway pressure (CPAP) vs intubation/surfactant. STUDY DESIGN: The Breathing Outcomes Study, a prospective secondary study to the Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial, assessed respiratory morbidity at 6-month intervals from hospital discharge to 18-22 months corrected age (CA). Two prespecified primary outcomes-wheezing more than twice per week during the worst 2-week period and cough longer than 3 days without a cold-were compared for each randomized intervention. RESULTS: One or more interviews were completed for 918 of the 922 eligible infants. The incidences of wheezing and cough were 47.9% and 31.0%, respectively, and did not differ between the study arms of either randomized intervention. Infants randomized to lower vs higher oxygen saturation targets had a similar risk of death or respiratory morbidity (except for croup and treatment with oxygen or diuretics at home). Infants randomized to CPAP vs intubation/surfactant had fewer episodes of wheezing without a cold (28.9% vs 36.5%; P<.05), respiratory illnesses diagnosed by a doctor (47.7% vs 55.2%; P<.05), and physician or emergency room visits for breathing problems (68.0% vs 72.9%; P<.05) by 18-22 months CA. CONCLUSION: Treatment with early CPAP rather than intubation/surfactant is associated with less respiratory morbidity by 18-22 months CA. Longitudinal assessment of pulmonary morbidity is necessary to fully evaluate the potential benefits of respiratory interventions for neonates.

The effects of umbilical cord milking on hemodynamics and neonatal outcomes in premature neonates.

OBJECTIVE: To determine whether umbilical cord milking (UCM) improves systemic blood flow and reduces neonatal morbidities compared with immediate cord clamping (ICC). STUDY DESIGN: Women admitted to a tertiary care center and delivering before 32 weeks' gestation were randomized to receive UCM or ICC. Three blinded serial echocardiograms were performed in the first 2 days of the infant's life. The primary outcome was measured systemic blood flow (superior vena cava flow) at each time point. RESULTS: Of the 60 neonates who were enrolled and randomized, 30 were assigned to cord milking and 30 to ICC. Neonates randomized to cord milking had greater measures of superior vena cava flow and right ventricular output in the first 6 hours and 30 hours of life. Neonates receiving UCM also had greater serum hemoglobin, received fewer blood transfusions, fewer days on oxygen therapy, and less frequent use of oxygen at 36 weeks' corrected postmenstrual age. CONCLUSIONS: We demonstrate greater systemic blood flow with UCM in preterm neonates compared with ICC. Future large prospective trials are needed to determine whether UCM reduces intraventricular hemorrhage and other long-term morbidities.

Quantitative end-tidal carbon dioxide monitoring in the delivery room: a randomized controlled trial.

OBJECTIVES: To investigate the utility of continuous quantitative end-tidal CO2 (Etco2) monitoring for managing assisted ventilation in the delivery room (DR). STUDY DESIGN: This is a prospective randomized controlled trial. Infants who received positive pressure ventilation (PPV) were randomized to a control versus a monitored arm. In the monitored arm, the resuscitating team adjusted PPV based on Etco2 values. In the control arm, the team provided PPV based on clinical assessment. Etco2 levels after resuscitation and admission Pco2 levels were compared between groups. RESULTS: Fifty infants were enrolled, and 48 subjects had primary outcome data. Of those, 7 infants were intubated in the DR, 41 infants received PPV via mask until respiratory support could be maintained on continuous positive airway pressure alone. The median Etco2 levels at the end of resuscitation were 44 mm Hg (16-66 mm Hg) in the control arm and 43 mm Hg (29-59 mm Hg) in the monitored arm. The proportion of Etco2 levels outside of the prespecified range was 52.6% (control) and 33.3% (monitored) (P = .236). The median admission Pco2 levels were 57 mm Hg (36-110 mm Hg) in the control arm and 55 mm Hg (40-93 mm Hg) in the monitored arm. The proportion of admission Pco2 levels outside of the prespecified range was 33.3% (control) versus 37.5% (monitored) (P = .763). CONCLUSIONS: Etco2 monitoring in the DR did not reduce the proportion of admission Pco2 levels outside of the prespecified range in a population of infants supported mostly with noninvasive ventilation.

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.

Empiric antifungal therapy and outcomes in extremely low birth weight infants with invasive candidiasis.

OBJECTIVE: To assess the impact of empiric antifungal therapy for invasive candidiasis on subsequent outcomes in premature infants. STUDY DESIGN: This was a cohort study of infants with a birth weight ≤ 1000 g receiving care at Neonatal Research Network sites. All infants had at least one positive culture for Candida. Empiric antifungal therapy was defined as receipt of a systemic antifungal on the day of or the day before the first positive culture for Candida was drawn. We created Cox proportional hazards and logistic regression models stratified on propensity score quartiles to determine the effect of empiric antifungal therapy on survival, time to clearance of infection, retinopathy of prematurity, bronchopulmonary dysplasia, end-organ damage, and neurodevelopmental impairment (NDI). RESULTS: A total of 136 infants developed invasive candidiasis. The incidence of death or NDI was lower in infants who received empiric antifungal therapy (19 of 38; 50%) compared with those who had not (55 of 86; 64%; OR, 0.27; 95% CI, 0.08-0.86). There was no significant difference between the groups for any single outcome or other combined outcomes. CONCLUSION: Empiric antifungal therapy was associated with increased survival without NDI. A prospective randomized trial of this strategy is warranted.

Cytokines and neurodevelopmental outcomes in extremely low birth weight infants.

OBJECTIVE: To determine if selected pro-inflammatory and anti-inflammatory cytokines and/or mediators of inflammation reported to be related to the development of cerebral palsy (CP) predict neurodevelopmental outcome in extremely low birth weight infants. STUDY DESIGN: Infants with birth weights ≤1000 g (n = 1067) had blood samples collected at birth and on days 3 ± 1, 7 ± 1, 14 ± 3, and 21 ± 3 to examine the association between cytokines and neurodevelopmental outcomes. The analyses were focused on 5 cytokines (interleukin [IL] 1ß; IL-8; tumor necrosis factor-α; regulated upon activation, normal T-cell expressed, and secreted (RANTES); and IL-2) reported to be most predictive of CP in term and late preterm infants. RESULTS: IL-8 was higher on days 0-4 and subsequently in infants who developed CP compared with infants who did not develop CP in both unadjusted and adjusted analyses. Other cytokines (IL-12, IL-17, tumor necrosis factor-ß, soluble IL rα, macrophage inflammatory protein 1ß) were found to be altered on days 0-4 in infants who developed CP. CONCLUSIONS: CP in former preterm infants may, in part, have a late perinatal and/or early neonatal inflammatory origin.

Shock: a common consequence of neonatal asphyxia.

Neonatal asphyxia is associated with multi-organ hypoxia-ischemia and subsequent dysfunction. The cardiovascular system is frequently affected, causing signs of shock and complicating the neonatal circulatory transition. Hypothermia therapy can improve outcome from neonatal asphyxia without adversely affecting cardiovascular stability. Therapy directed at the cardiovascular system can improve short-term measures of systemic blood flow, but to date has not been demonstrated to improve long-term outcome.

Neonatal intubation: success of pediatric trainees.

OBJECTIVES: To review the success of pediatric trainees for neonatal intubation over a 10-year interval at a single academic center. STUDY DESIGN: We reviewed a database of all neonatal intubations designed as a quality assurance process at our institution. Respiratory care practitioners recorded the number of attempts at the time of each procedure. Attempts were defined as each time a laryngoscope was placed in the baby's mouth. Success rates were calculated as the number of successful intubations divided by the attempts. RESULTS: From January 1992 through September 2002, 5051 successful intubations with 9190 attempts were performed by all practitioners. Pediatric residents intubated neonates successfully on 1676 occasions requiring 3719 attempts. The median success rates were 33% for pediatric level (PL)1 residents; 40% for PL2 and PL3 residents, and 68% for neonatal fellows ( P < .001). The success rates for residents who had more than 20 total attempts versus those who had fewer than 20 attempts were 49% versus 37% ( P < .001). CONCLUSIONS: Developing proficiency at intubation requires a significant amount of experience. Current pediatric residents at our institution have inadequate opportunity to achieve consistent success.