Objective To assess whether providing ventilation during delayed cord clamping (V-DCC) increases placental transfusion compared with delayed cord clamping alone (DCC only). Study design Inborn ...premature infants (230/7 -316/7 weeks' gestational age) were randomized to receive at least 60 seconds of V-DCC (initial continuous positive airway pressure) with addition of positive pressure ventilation if needed) or without assisted ventilation (DCC only). For the DCC-only group, infants were dried and stimulated by gently rubbing the back if apneic. The primary outcome was the peak hematocrit in the first 24 hours of life. Delivery room outcomes were analyzed from video recordings and a data acquisition system. Hemodynamic measurements were performed with the use of functional echocardiography, near-infrared spectroscopy, and electrical cardiometry. Results There was no difference in the primary outcome of peak hematocrit in the first 24 hours of life. The onset of breathing was similar between both groups (25 ± 20 and 27 ± 28 seconds, P = .627); however, infants receiving DCC received a greater duration of stimulation than V-DCC (41 ± 19 and 20 ± 21 seconds P = .002). There were no differences in delivery room interventions, early hemodynamics (cerebral oxygenation by near-infrared spectroscopy, cardiac output and stroke volume by electrical cardiometry, or superior vena cava flow by of functional echocardiography), or neonatal outcomes. Conclusions V-DCC was feasible but did not lead to any measurable clinical improvements immediately after delivery or reduce subsequent neonatal morbidity. Caretakers should consider providing adequate stimulation before cord clamping. Trial registration ClinicalTrials.gov : NCT02231411.
Objective To evaluate whether neonates exposed to multiple intubation attempts within the first 4 days after birth have an increased incidence of intraventricular hemorrhage (IVH). Study design This ...is a retrospective cohort study of infants intubated during the first 4 days after birth. Infants had birth weights (BWs) less than 1500 g and were admitted to the neonatal intensive care unit (NICU) at the University of California, San Diego, between January 1, 2005, and July 30, 2009. A subgroup analysis was done for infants with BW less than 750 g. Results A total of 308 infants with BW <1500 g, including 102 with a BW <750 g, were intubated within the first 4 days of life. The number of intubation attempts was significantly greater in infants with a BW <750 g who had severe IVH compared with those with mild or no IVH (OR 1.395, 95% CI 1.090-1.786, P = .008). For infants with BW <1500 g, the number of intubation attempts in the delivery room was significantly greater for infants with severe IVH (OR 1.317, 95% CI 1.052-1.649, P = .016). Conclusion Increased intubation attempts were associated with increased incidence of severe IVH in infants with BW less than 750 g and in infants less than 1500 g who were intubated only in the delivery room. Prospective studies are needed to further evaluate the relationship between intubation attempts and severe IVH.
Objective Retinopathy of prematurity (ROP), a vasoproliferative disorder of the retina in preterm infants, is associated with multiple factors, including oxygenation level. We explored whether the ...common intermittent hypoxemic events in preterm infants are associated with the development of ROP. Study design Oxygen desaturation events were quantified in 79 preterm infants (gestational age, 24 to 27-6/7 weeks) during the first 8 weeks of life. Infants were classified as requiring laser treatment for ROP versus having less severe or no ROP. A linear mixed model was used to study the association between the incidence of intermittent hypoxia and laser treatment of ROP, controlling for gestational age, sex, race, multiple births, and initial severity of illness. Results For all infants, hypoxemic events increased with postnatal age ( P < .001). Controlling for all covariates, a higher incidence of oxygen desaturation events was found in the infants undergoing laser therapy for ROP ( P < .001), males ( P < .02), and infants of younger gestational age ( P < .003). Conclusions The incidence of hypoxemic events was higher in infants with ROP requiring laser therapy. Therapeutic strategies to optimize oxygenation in preterm infants should include minimization of desaturation episodes, which may in turn decrease serious morbidity in this high-risk population.
Objective To test the hypothesis that preterm infants randomized to a low vs high O2 saturation target range have a higher incidence of intermittent hypoxemia. Study design A subcohort of 115 preterm ...infants with high resolution pulse oximetry enrolled in the Surfactant, Positive Pressure, and Oxygenation Randomized Trial were randomized to low (85%-89%) or high (91%-95%) O2 saturation target ranges. Oxygen saturation was monitored until 36 weeks postmenstrual age or until the infant was breathing room air without respiratory support for ≥72 hours. Results The low target O2 saturation group had a higher rate of intermittent hypoxemia (≤80% for ≥10 seconds and ≤3 minutes) prior to 12 days and beyond 57 days of life ( P < .05). The duration shortened ( P < .0001) and the severity increased ( P < .0001) with increasing postnatal age with no differences between target saturation groups. The higher rate of intermittent hypoxemia events in the low target group was associated with a time interval between events of <1 minute. Conclusion A low O2 saturation target was associated with an increased rate of intermittent hypoxemia events that was dependent on postnatal age. The duration and severity of events was comparable between target groups. Further investigation is needed to assess the role of intermittent hypoxemia and their timing on neonatal morbidity.
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.
Objective To determine whether resuscitation teams can better maintain newborn transitional oxygen saturation (SpO2 ) values within a prespecified target range using a graphical display of the ...targets and real-time SpO2 data compared with using only numerical oximeter values. Study design Preterm neonates were enrolled in this prospective cohort evaluation of a change in practice. The Transitional Oxygen Targeting System (TOTS) plots real-time SpO2 values in relation to 10th and 50th percentile SpO2 curves, which provides a visual target. After introduction of the TOTS, the resuscitation team adjusted the fraction of inspired oxygen to maintain the SpO2 within the target range, and before its use neonates were resuscitated in attempt to target normal transitional SpO2 values without using the TOTS monitor. Duration of time within 10th-50th percentile values was compared between 2 cohorts, children evaluated with the TOTS and those not evaluated with the TOTS (controls). Results A total of 40 infants were enrolled, including 20 prospectively evaluated with the TOTS and 20 controls. Mean gestational age, birth weight, total resuscitation time, duration of supplemental oxygen administration, changes in oxygen concentration, and respiratory support provided were similar in the 2 groups. The TOTS cohort spent 52% of time within the target range; the control cohort, 37% ( P = .03). Conclusion SpO2 values were maintained within a specified target range for significantly longer in preterm neonates resuscitated using the TOTS display compared with those resuscitated without TOTS.
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.
Objectives To investigate the utility of continuous quantitative end-tidal CO2 (Et co2 ) 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 Et co2 values. In the control arm, the team provided PPV based on clinical assessment. Et co2 levels after resuscitation and admission P co2 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 Et co2 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 Et co2 levels outside of the prespecified range was 52.6% (control) and 33.3% (monitored) ( P = .236). The median admission P co2 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 P co2 levels outside of the prespecified range was 33.3% (control) versus 37.5% (monitored) ( P = .763). Conclusions Et co2 monitoring in the DR did not reduce the proportion of admission P co2 levels outside of the prespecified range in a population of infants supported mostly with noninvasive ventilation.
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 1β; 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-β, soluble IL rα, macrophage inflammatory protein 1β) 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.
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