REUNION BIBLIOGRAFICA

1. REUNION BIBLIOGRAFICA • Pediatric Academic Societies • Annual Meeting • Mayo 4 – 7 • Washington. DC • Criterio Búqueda: Neonatal Clinical Trial • Criterio Selección: Arbitrario

2. Temas Relevantes del Meeting • Reanimación • Diseño Unidades • RNM seguimiento • Nariceras / CPAP • Oxígeno – Saturación. • Sepsis precoz - Profilaxis

3.  The Incidence and Impact of CMV Infection in Preterm InfantsKristen M. Turner, Henry C. Lee, Suresh B. Boppana, Waldemar A. Carlo, David A. Randolph. Pediatrics, University of Alabama, Birmingham, Birmingham, AL; Pediatrics, University of California, San Francisco, San Francisco, CA. • BACKGROUND: Congenital cytomegalovirus (CMV) is the leading cause of non-genetic deafness in children in the U.S. and can cause neurodevelopmental impairment (NDI) in term infants. Limited data exist regarding whether congenital CMV is associated with preterm delivery. The extent to which CMV infection increases the risk of adverse outcomes in very low birth weight (VLBW) preterm infants is also unknown.

4. OBJECTIVE: We aimed to determine the incidence of congenital CMV in VLBW infants, and to describe and role of congenital and acquired CMV in modifying outcomes of VLBW preterm infants. • DESIGN/METHODS: • This was a retrospective case controlled study of infants admitted to the • UAB nursery where CMV screening is part of routine admission orders. • All infants admitted between the years 1993-2008 and weighing <1500 grams were • included. • CMV status and clinical outcomes were queried using two internal patient • databases and hospital-based medical records. For clinical outcomes • analysis, the 5 consecutive VLBW infants born before and after each • CMV-positive case were used as controls. The primary outcome was • death or NDI. Secondary outcomes included sensorineural hearing loss, • intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary • dysplasia, necrotizing enterocolitis, retinopathy of prematurity, and culture proven • late-onset sepsis. Multivariate analysis was performed.

5. RESULTS: • 17 of 4,594 VLBW infants had congenital CMV (0.37%) (a lower rate than published for term infants). • 16 infants (0.35%) acquired CMV in the nursery. • Compared to controls, congenitally infected VLBW infants were more likely to have hearing loss (64% vs. 10%, p<0.0001) and abnormal neuroimaging (71% vs. 28%, p<0.0001). Developmental motor outcomes were also significantly worse for CMV infected infants (50% vs. 12%, p=0.03), although this information was available for only 33 controls and 6 congenital CMV infants. Congenital CMV was not associated with death. • Acquired CMV was only associated with gastrointestinal perforation (p=0.008). • CONCLUSIONS: • CMV infection is not positively associated with prematurity. • Congenital but not acquired CMV in VLBW infants is associated with • hearing loss and neurologic deficits.

6. Inhaled Nitric Oxide Usage in the NICHD Neonatal Research Network: Inter-Site Variability and Propensity EvaluationWilliam Truog, • BACKGROUND: • The appropriate use of inhaled nitric oxide (INO) in preterm infants • remains controversial even after multiple clinical trials. • In October 2010, an NIH Consensus Development Conference report • cautioned against routine use of INO in infants <34 weeks gestation. • OBJECTIVE: To determine variability in Center use of INO in the • NICHD Neonatal Research Network (NRN) before and after the • consensus conference and to examine associations between INO use • and the outcomes of severe BPD or death.

7. DESIGN/METHODS: • The NICHD NRN Generic Database for 2008-2011 collects data including INO use on infants <29 weeks GA or <1000 gram birthweight. A total of 13 centers contributed data across this time period and INO use starting between days 1-6 and 7-28 was noted for each center. A propensity evaluation focusing on the 7-28 day group with risk-matching by pre-identified variables (center, GA, BW, gender, SGA status, antenatal steroids, 5 minute Apgar, DR resuscitation, multiple gestation, and prenatal care) was undertaken to assess the outcome of severe BPD or death in infants treated with INO and risk matched infants not treated. Severe BPD is PPV or FIO2>0.3 at 36 weeks PMA.

8. RESULTS: • A total of 4,757 infants were assessed for the 4-year period (3,635 for 2008-2010 and 1,122 for 2011). • 196 (3.3%) infants received INO between day 1 and 6. • 187 (3.3%) infants between days 7 and 28 • 84 (1.3%) >28 days. • Center-specific frequency of INO use during 2008-2010 ranged from 21.9% to 0.4%, median 3.5%. • There was a decrease in use for CY 2011 compared to 2008-2010 for infants age ≥7 days with 12 of 13 sites demonstrating reduced usage; overall NRN decrease in usage was from 4.6% to 1.6% (RR 0.246, p<0.001). • The propensity study demonstrated that INO use, started between 7-28 days, was associated with severe BPD or death, adjusted OR 2.3, 95% CI: 1.5-3.6.

9. CONCLUSIONS: • Substantial variability in INO use for extremely preterm infants existed across the NRN centers. • Both total use and variability decreased in 2011, possibly reflecting the consensus conference. • As expected, INO use started at 7-28 days was associated with more severe outcomes. • The specific contribution of INO usage to outcome cannot be inferred from propensity analysis.

10.  Comparison of Devices for Newborn Mask Ventilation in the Delivery Room. the DVD Trial: Multicenter Cluster-Randomized Two Period Crossover Trial • Edgardo Szyld, Adriana Aguilar, Gabriel Musante, Nestor Vain, Luis Prudent, Jorge Fabres, Waldemar Carlo. FUNDASAMIN-Fundacion Para la Salud Materno Infantil, Buenos Aires, Argentina; Hospital Diego Paroissien, Buenos Aires, Argentina; Hospital Universitario Austral, Pilar, Buenos Aires, Argentina; Division of Pediatrics, Pontificia Universidad Catolica de Chile, Santiago, Chile; University of Alabama at Birmingham, Birmingham, AL. • BACKGROUND: Self inflating bags (SIB) are the most commonly used devices for manual ventilation worldwide. Although the use of T-piece resuscitators (TP) is increasing, no large randomized controlled trials have compared their effectiveness and safety. • OBJECTIVE: To compare the effectiveness of TP and SIB in achieving a heart rate ≥ 100 bpm in depressed newborns (NB) after the initiation of positive pressure ventilation (PPV) with face mask after birth

11. DESIGN/METHODS: • Multicenter, cluster-randomized, two period crossover trial conducted in 11 sites (4 in Argentina, 3 in Chile, 2 in USA, 1 in Italy and 1 in Peru). • NB ≥ 26 weeks of gestational age (GA) requiring PPV at birth per NRP guidelines were included. PPV was provided with either a SIB [SIB group] with and without PEEP valve or a TP with PEEP [TP group] in two randomly sequenced periods for each center. Initial target: PIP 25 cm H2O and PEEP of 5 cm H2O when used. • RESULTS: From Dec 2009 to Aug 2012, 1032 NB were enrolled and 1027 were available for analysis by intention to treat. Baseline characteristics were comparable between groups except for the distribution of NB <1500g (17% TP vs. 21% SIB). A similar proportion of NB achieved a HR ≥ 100 bpm at 2 minutes after birth in the TP and SIB groups. There were no deaths in the DR.

12. CONCLUSIONS: In NB ≥ 26 GA, PPV using face mask with either TP or SIB showed similar effect in achieving a HR ≥ 100 bpm at 2 min after birth.

13. High-Flow Nasal Cannulae vs. Nasal CPAP for Post-Extubation Respiratory Support of Very Preterm Infants: A Multicenter, Randomized, Non-Inferiority Trial • BACKGROUND: High-flow nasal cannulae (HFNC) are an increasingly popular alternative to nasal continuous positive airway pressure (NCPAP) for non-invasive respiratory support of preterm infants. However, little evidence exists for the efficacy or safety of HFNC in the preterm population. • OBJECTIVE: We aimed to determine if HFNC was non-inferior to NCPAP as post-extubation respiratory support for very preterm infants less than 32 weeks' of gestational age (GA).

14. DESIGN/METHODS: • A total of 303 very preterm infants from three Australian tertiary • perinatal centers were randomized at first extubation to receive • either HFNC 5-6 Liters per minute or NCPAP 7 centimeters of • water (cm H2O) as post-extubation support. Pre-randomization • stratification was by GA (<26 weeks', 26 weeks' or more) and • center. The primary outcome was failure of the assigned treatment • within 7 days of extubation, using pre-specified failure criteria. The • pre-defined margin of non-inferiority for HFNC was 20%. A sample • size of 300 infants was sufficient to demonstrate non-inferiority of • HFNC with 87% power. Infants in whom HFNC failed could receive • 'rescue' NCPAP 7 cm H2O; if they again satisfied the failure criteria • during the primary outcome period they were re-intubated. The • NCPAP group were re-intubated if failure occurred. Infants were • followed until discharge home from hospital.

15. RESULTS: • The mean GA and birth weight of the HFNC and NCPAP groups were 27.7 weeks, 1041g and 27.5 weeks, 1044g respectively. • HFNC was non-inferior to NCPAP: failure of assigned treatment occurred in 52/152 (34.2%) of the HFNC group and 39/151 (25.8%) of the NCPAP group, risk difference (95% CI) 8.4 (-1.9, 18.7)%. • In infants <26 weeks' GA, the risk difference (95% CI) was 20.0 (-1.9, 41.8)%. • Overall, almost half of infants in whom HFNC failed were 'rescued' from re-intubation by NCPAP: 27/152 (17.8%) of the HFNC group were re-intubated during the primary outcome period, compared to 38/151 (25.2%) of the NCPAP group. • There was significantly less nasal trauma in the HFNC group (P=0.009), but no differences in the incidence of any other secondary outcomes including death, bronchopulmonary dysplasia or pneumothorax. • CONCLUSIONS: HFNC therapy is safe and non-inferior to NCPAP as post-extubation respiratory support in very preterm infants, and causes less nasal trauma.

16.  A Randomized Controlled Trial of Two Levels of Nasal CPAP for Extubation in Preterm InfantsBridget Buzzella, Nelson Claure, Carmen D'Ugard, Eduardo Bancalari. Division of Neonatology-Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL. • BACKGROUND: Nasal CPAP is routinely used after extubation in preterm infants. However, there is paucity of data on the most effective and safe level of NCPAP in these infants. • OBJECTIVE: To compare two levels of NCPAP during the post-extubation period in preterm infants with residual lung disease in a randomized controlled trial. • DESIGN/METHODS: Mechanically ventilated preterm infants of BW 500-1000 g and GA 23-30 w, extubated for the first time during the first 6 weeks and requiring ≥ 25% O2 at the time of extubation, were randomly assigned to Low-NCPAP of 5 (range 4-6) or High-NCPAP of 8 (range 7-9) cmH2O. Infants remained in the assigned NCPAP range for 96 hours after extubation.

17. RESULTS: 93 infants extubated at postnatal day 16 ± 14 were randomized to Low (n=47) or High NCPAP (n=46). BW, GA, ventilator settings and FiO2 did not differ between groups at randomization. The rates of extubation failure according to pre-established criteria or need for re-intubation during the 96 hours post extubation were significantly lower in the High compared to the Low NCPAP group. This was mainly due to a striking reduction in the failure rate in the 500-750 g BW strata. The rates of BPD (O2 at 36w) or severe BPD (O2≥30%, NCPAP or IPPV at 36w) did not differ significantly. No infant developed a pneumothorax during the 96 h post-extubation period.

18. CONCLUSIONS: In preterm infants who require ≥ 25 % O2 at the time of extubation, NCPAP of 8 (range 7-9) significantly reduced extubation failure compared to the conventional level of 5 (range 4-6) cmH2O. The advantage of the higher NCPAP was more striking in the smaller infants. This suggests the need for higher distending airway pressures post-extubation in the more immature infants with residual lung disease. These results cannot be extrapolated to infants with early RDS or no lung disease.