Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Infants.

BACKGROUND: Limited data suggest that higher hemoglobin thresholds for red-cell transfusions may reduce the risk of cognitive delay among extremely-low-birth-weight infants with anemia. METHODS: We performed an open, multicenter trial in which infants with a birth weight of 1000 g or less and a gestational age between 22 weeks 0 days and 28 weeks 6 days were randomly assigned within 48 hours after delivery to receive red-cell transfusions at higher or lower hemoglobin thresholds until 36 weeks of postmenstrual age or discharge, whichever occurred first. The primary outcome was a composite of death or neurodevelopmental impairment (cognitive delay, cerebral palsy, or hearing or vision loss) at 22 to 26 months of age, corrected for prematurity. RESULTS: A total of 1824 infants (mean birth weight, 756 g; mean gestational age, 25.9 weeks) underwent randomization. There was a between-group difference of 1.9 g per deciliter (19 g per liter) in the pretransfusion mean hemoglobin levels throughout the treatment period. Primary outcome data were available for 1692 infants (92.8%). Of 845 infants in the higher-threshold group, 423 (50.1%) died or survived with neurodevelopmental impairment, as compared with 422 of 847 infants (49.8%) in the lower-threshold group (relative risk adjusted for birth-weight stratum and center, 1.00; 95% confidence interval [CI], 0.92 to 1.10; P = 0.93). At 2 years, the higher- and lower-threshold groups had similar incidences of death (16.2% and 15.0%, respectively) and neurodevelopmental impairment (39.6% and 40.3%, respectively). At discharge from the hospital, the incidences of survival without severe complications were 28.5% and 30.9%, respectively. Serious adverse events occurred in 22.7% and 21.7%, respectively. CONCLUSIONS: In extremely-low-birth-weight infants, a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity. (Funded by the National Heart, Lung, and Blood Institute and others; TOP ClinicalTrials.gov number, NCT01702805.).

Neurodevelopmental outcomes of very preterm infants who received cord milking at birth: a randomized controlled trial.

Umbilical cord milking improves postnatal adaptation and short-term outcomes of very preterm infants compared to early cord clamping. Little is known about the impact of umbilical cord milking on long-term neurodevelopmental outcomes. The objective of this study is to compare the effects of intact umbilical cord milking (UCM) vs. early cord clamping (ECC) at birth on neurodevelopmental outcomes at 36 months' corrected age. Preterm infants < 31 weeks' gestation who were randomized at birth to receive three time milking of their attached cord or ECC (< 10 s) were evaluated at 36 months' corrected age. Neurodevelopmental outcomes were assessed by blinded examiners using Bayley Scales of Infant and Toddler Development (version III). Analysis was by intention to treat. Out of the 73 infants included in the original trial, 2 died and 65 (92%) infants were evaluated at 36 months' corrected age. Patient characteristics and short-term outcomes were similar in both study groups. There were no significant differences in the median cognitive, motor or language scores or in the rates of cerebral palsy, developmental impairment, deafness, or blindness between study groups. CONCLUSION: Neurodevelopmental outcomes at 36 months' corrected age of very preterm infants who received UCM were not shown to be significantly different from those who received ECC at birth. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01487187 What is Known: • Compared to early cord clamping, umbilical cord milking improves postnatal adaptation and short-term outcomes of very preterm infants compared to early cord clamping. • Little is known about the impact of umbilical cord milking on neurodevelopmental outcomes. WHAT IS NEW: • Neurodevelopmental outcomes at 3 years of age were not significantly different in very preterm infants who received cord milking vs. those who received early cord clamping at birth.

Association between Intermittent Hypoxemia and Severe Bronchopulmonary Dysplasia in Preterm Infants.

Rationale: Bronchopulmonary dysplasia increases the risk of disability in extremely preterm infants. Although the pathophysiology remains uncertain, prior exposure to intermittent hypoxemia may play a role in this relationship. Objectives: To determine the association between prolonged episodes of intermittent hypoxemia and severe bronchopulmonary dysplasia. Methods: A post hoc analysis of extremely preterm infants in the Canadian Oxygen Trial who survived to 36 weeks' postmenstrual age was performed. Oxygen saturations <80% for ⩾1 minute and the proportion of time per day with hypoxemia were quantified using continuous pulse oximetry data that had been sampled every 10 seconds from within 24 hours of birth until 36 weeks' postmenstrual age. The study outcome was severe bronchopulmonary dysplasia as defined in the 2001 NIH Workshop Summary. Measurements and Main Results: Of 1,018 infants, 332 (32.6%) developed severe bronchopulmonary dysplasia. The median number of hypoxemic episodes ranged from 0.8/day (interquartile range, 0.2-1.1) to 60.2/day (interquartile range, 51.4-70.3) among the least and most affected 10% of infants. Compared with the lowest decile of exposure to hypoxemic episodes, the adjusted relative risk of severe bronchopulmonary dysplasia increased progressively from 1.72 (95% confidence interval, 1.55-1.90) at the 2nd decile to 20.40 (95% confidence interval, 12.88-32.32) at the 10th decile. Similar risk gradients were observed for time in hypoxemia. Significant differences in the rates of hypoxemia between infants with and without severe bronchopulmonary dysplasia emerged within the first week after birth. Conclusions: Prolonged intermittent hypoxemia beginning in the first week after birth was associated with an increased risk of developing severe bronchopulmonary dysplasia among extremely preterm infants. Clinical trial registered with www.isrctn.com (ISRCTN62491227) and www.clinicaltrials.gov (NCT00637169).

Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-analysis Collaboration.

Importance: There are potential benefits and harms of hyperoxemia and hypoxemia for extremely preterm infants receiving more vs less supplemental oxygen. Objective: To compare the effects of different target ranges for oxygen saturation as measured by pulse oximetry (Spo2) on death or major morbidity. Design, Setting, and Participants: Prospectively planned meta-analysis of individual participant data from 5 randomized clinical trials (conducted from 2005-2014) enrolling infants born before 28 weeks' gestation. Exposures: Spo2 target range that was lower (85%-89%) vs higher (91%-95%). Main Outcomes and Measures: The primary outcome was a composite of death or major disability (bilateral blindness, deafness, cerebral palsy diagnosed as ≥2 level on the Gross Motor Function Classification System, or Bayley-III cognitive or language score <85) at a corrected age of 18 to 24 months. There were 16 secondary outcomes including the components of the primary outcome and other major morbidities. Results: A total of 4965 infants were randomized (2480 to the lower Spo2 target range and 2485 to the higher Spo2 range) and had a median gestational age of 26 weeks (interquartile range, 25-27 weeks) and a mean birth weight of 832 g (SD, 190 g). The primary outcome occurred in 1191 of 2228 infants (53.5%) in the lower Spo2 target group and 1150 of 2229 infants (51.6%) in the higher Spo2 target group (risk difference, 1.7% [95% CI, -1.3% to 4.6%]; relative risk [RR], 1.04 [95% CI, 0.98 to 1.09], P = .21). Of the 16 secondary outcomes, 11 were null, 2 significantly favored the lower Spo2 target group, and 3 significantly favored the higher Spo2 target group. Death occurred in 484 of 2433 infants (19.9%) in the lower Spo2 target group and 418 of 2440 infants (17.1%) in the higher Spo2 target group (risk difference, 2.8% [95% CI, 0.6% to 5.0%]; RR, 1.17 [95% CI, 1.04 to 1.31], P = .01). Treatment for retinopathy of prematurity was administered to 220 of 2020 infants (10.9%) in the lower Spo2 target group and 308 of 2065 infants (14.9%) in the higher Spo2 target group (risk difference, -4.0% [95% CI, -6.1% to -2.0%]; RR, 0.74 [95% CI, 0.63 to 0.86], P < .001). Severe necrotizing enterocolitis occurred in 227 of 2464 infants (9.2%) in the lower Spo2 target group and 170 of 2465 infants (6.9%) in the higher Spo2 target group (risk difference, 2.3% [95% CI, 0.8% to 3.8%]; RR, 1.33 [95% CI, 1.10 to 1.61], P = .003). Conclusions and Relevance: In this prospectively planned meta-analysis of individual participant data from extremely preterm infants, there was no significant difference between a lower Spo2 target range compared with a higher Spo2 target range on the primary composite outcome of death or major disability at a corrected age of 18 to 24 months. The lower Spo2 target range was associated with a higher risk of death and necrotizing enterocolitis, but a lower risk of retinopathy of prematurity treatment.

Benefits of Oxygen Saturation Targeting Trials: Oximeter Calibration Software Revision and Infant Saturations.

It has been reported in the 3 Benefits of Oxygen Saturation Targeting (BOOST-II) trials that changes in oximeter calibration software resulted in clearer separation between the oxygen saturations in the two trial target groups. A revised analysis of the published BOOST-II data does not support this conclusion.

The Effect of Skin Pigmentation on the Accuracy of Pulse Oximetry in Infants with Hypoxemia.

To compare pulse oximetry measurement bias between infants with hypoxemia with either dark skin or light skin with Masimo Radical 7 and Nellcor Oximax. There was no significant difference in systematic bias based on skin pigment for either oximeter.

Effects of targeting lower versus higher arterial oxygen saturations on death or disability in preterm infants.

BACKGROUND: The use of supplemental oxygen in the care of extremely preterm infants has been common practice since the 1940s. Despite this, there is little agreement regarding which oxygen saturation (SpO2) ranges to target to maximise short- or long-term growth and development, while minimising harms. There are two opposing concerns. Lower oxygen levels (targeting SpO2 at 90% or less) may impair neurodevelopment or result in death. Higher oxygen levels (targeting SpO2 greater than 90%) may increase severe retinopathy of prematurity or chronic lung disease.The use of pulse oximetry to non-invasively assess neonatal SpO2 levels has been widespread since the 1990s. Until recently there were no randomised controlled trials (RCTs) that had assessed whether it is better to target higher or lower oxygen saturation levels in extremely preterm infants, from birth or soon thereafter. As a result, there is significant international practice variation and uncertainty remains as to the most appropriate range to target oxygen saturation levels in preterm and low birth weight infants. OBJECTIVES: 1. What are the effects of targeting lower versus higher oxygen saturation ranges on death or major neonatal and infant morbidities, or both, in extremely preterm infants?2. Do these effects differ in different types of infants, including those born at a very early gestational age, or in those who are outborn, without antenatal corticosteroid coverage, of male sex, small for gestational age or of multiple birth, or by mode of delivery? SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 4), MEDLINE via PubMed (1966 to 11 April 2016), Embase (1980 to 11 April 2016) and CINAHL (1982 to 11 April 2016). We also searched clinical trials databases, conference proceedings and the reference lists of retrieved articles for randomised controlled trials. SELECTION CRITERIA: Randomised controlled trials that enrolled babies born at less than 28 weeks' gestation, at birth or soon thereafter, and targeted SpO2 ranges of either 90% or below or above 90% via pulse oximetry, with the intention of maintaining such targets for at least the first two weeks of life. DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane Neonatal to extract data from the published reports of the included studies. We sought some additional aggregate data from the original investigators in order to align the definitions of two key outcomes. We conducted the meta-analyses with Review Manager 5 software, using the Mantel-Haenszel method for estimates of typical risk ratio (RR) and risk difference (RD) and a fixed-effect model. We assessed the included studies using the Cochrane 'Risk of bias' and GRADE criteria in order to establish the quality of the evidence. We investigated heterogeneity of effects via pre-specified subgroup and sensitivity analyses. MAIN RESULTS: Five trials, which together enrolled 4965 infants, were eligible for inclusion. The investigators of these five trials had prospectively planned to combine their data as part of the NeOProM (Neonatal Oxygen Prospective Meta-analysis) Collaboration. We graded the quality of evidence as high for the key outcomes of death, major disability, the composite of death or major disability, and necrotising enterocolitis; and as moderate for blindness and retinopathy of prematurity requiring treatment.When an aligned definition of major disability was used, there was no significant difference in the composite primary outcome of death or major disability in extremely preterm infants when targeting a lower (SpO2 85% to 89%) versus a higher (SpO2 91% to 95%) oxygen saturation range (typical RR 1.04, 95% confidence interval (CI) 0.98 to 1.10; typical RD 0.02, 95% CI -0.01 to 0.05; 5 trials, 4754 infants) (high-quality evidence). Compared with a higher target range, a lower target range significantly increased the incidence of death at 18 to 24 months corrected age (typical RR 1.16, 95% CI 1.03 to 1.31; typical RD 0.03, 95% CI 0.01 to 0.05; 5 trials, 4873 infants) (high-quality evidence) and necrotising enterocolitis (typical RR 1.24, 95% 1.05 to 1.47; typical RD 0.02, 95% CI 0.01 to 0.04; 5 trials, 4929 infants; I² = 0%) (high-quality evidence). Targeting the lower range significantly decreased the incidence of retinopathy of prematurity requiring treatment (typical RR 0.72, 95% CI 0.61 to 0.85; typical RD -0.04, 95% CI -0.06 to -0.02; 5 trials, 4089 infants; I² = 69%) (moderate-quality evidence). There were no significant differences between the two treatment groups for major disability including blindness, severe hearing loss, cerebral palsy, or other important neonatal morbidities.A subgroup analysis of major outcomes by type of oximeter calibration software (original versus revised) found a significant difference in the treatment effect between the two software types for death (interaction P = 0.03), with a significantly larger treatment effect seen for those infants using the revised algorithm (typical RR 1.38, 95% CI 1.13 to 1.68; typical RD 0.06, 95% CI 0.01 to 0.10; 3 trials, 1716 infants). There were no other important differences in treatment effect shown by the subgroup analyses using the currently available data. AUTHORS' CONCLUSIONS: In extremely preterm infants, targeting lower (85% to 89%) SpO2 compared to higher (91% to 95%) SpO2 had no significant effect on the composite outcome of death or major disability or on major disability alone, including blindness, but increased the average risk of mortality by 28 per 1000 infants treated. The trade-offs between the benefits and harms of the different oxygen saturation target ranges may need to be assessed within local settings (e.g. alarm limit settings, staffing, baseline outcome risks) when deciding on oxygen saturation targeting policies.

Effects of Targeting Higher or Lower Oxygen Saturations in Centers with More Versus Less Separation between Median Saturations.

Subgroup analysis of the Canadian Oxygen Trial to compare outcomes of extremely preterm infants in centers with more versus less separation between median arterial oxygen saturations in the two target ranges. Centers with more separation observed lower rates of death or disability in the 85%-89% range than in the 91%-95% target range.

An Algorithm for Predicting Neonatal Mortality in Threatened Very Preterm Birth.

OBJECTIVE: To develop a prediction model for neonatal mortality using information readily available in the antenatal period. METHODS: A multiple logistic regression model of a complete population-based geographically defined cohort of very preterm infants of 23+0 to 30+6 weeks' gestation was used to identify antenatal factors which were predictive of mortality in this population. Infants lt; 23 weeks and those with major anomalies were excluded. RESULTS: Between 1996 and 2012, 1240 live born infants lt; 31 weeks' gestation were born to women residing in Nova Scotia. Decreasing gestational age strongly predicted an increased mortality rate. Other factors significantly contributing to increased mortality included classification as small for gestational age, oligohydramnios, maternal psychiatric disorders, antenatal antibiotic therapy, and monochorionic twins. Reduced neonatal mortality was associated with antenatal use of antihypertensive agents and use of corticosteroids of any duration of therapy given at least 24 hours before delivery. An algorithm was developed to estimate the risk of mortality without the need for a calculator. CONCLUSION: Prediction of the probability of neonatal mortality is influenced by maternal and fetal factors. An algorithm to estimate the risk of mortality facilitates counselling and informs shared decision making regarding obstetric management.

Objectif : Élaborer un modèle prédictif en ce qui concerne la mortalité néonatale au moyen de renseignements faciles à obtenir au cours de la période prénatale. Méthodes : Nous avons eu recours au modèle de régression logistique multiple d'une cohorte exhaustive, populationnelle et définie géographiquement de nouveau-nés très prématurés (âge gestationnel : de 23+0 à 30+6 semaines) pour identifier les facteurs prénataux permettant de prédire la mortalité au sein de cette population. Les nouveau-nés dont l'âge gestationnel était inférieur à 23 semaines et ceux qui présentaient des anomalies majeures ont été exclus. Résultats : Entre 1996 et 2012, 1 240 enfants nés vivants à moins de 31 semaines de gestation ont été issus de femmes résidant en Nouvelle-Écosse. La baisse de l'âge gestationnel constituait un facteur solide permettant de prédire une hausse du taux de mortalité. Parmi les autres facteurs contribuant de façon significative à la hausse du taux de mortalité, on trouvait l'hypotrophie fœtale, l'oligohydramnios, les troubles psychiatriques maternels, l'antibiothérapie prénatale et les jumeaux monozygotes. La baisse du taux de mortalité néonatale était associée à l'utilisation prénatale d'antihypertenseurs et à l'utilisation de corticostéroïdes (peu importe la durée du traitement) administrés au moins 24 heures avant l'accouchement. Nous avons élaboré un algorithme pour estimer le risque de mortalité sans avoir recours à une calculatrice. Conclusion : La prévision de la probabilité de la mortalité néonatale est influencée par des facteurs maternels et fœtaux. Le fait de disposer d'un algorithme pour estimer le risque de mortalité facilite le counseling et éclaire le processus décisionnel partagé en ce qui concerne la prise en charge obstétricale.

Association Between Intermittent Hypoxemia or Bradycardia and Late Death or Disability in Extremely Preterm Infants.

IMPORTANCE: Extremely preterm infants may experience intermittent hypoxemia or bradycardia for many weeks after birth. The prognosis of these events is uncertain. OBJECTIVE: To determine the association between intermittent hypoxemia or bradycardia and late death or disability. DESIGN, SETTING, AND PARTICIPANTS: Post hoc analysis of data from the inception cohort assembled for the Canadian Oxygen Trial in 25 hospitals in Canada, the United States, Argentina, Finland, Germany, and Israel, including 1019 infants with gestational ages of 23 weeks 0 days through 27 weeks 6 days who were born between December 2006 and August 2010 and survived to a postmenstrual age of 36 weeks. Follow-up assessments occurred between October 2008 and August 2012. EXPOSURES: Episodes of hypoxemia (pulse oximeter oxygen saturation <80%) or bradycardia (pulse rate <80/min) for 10 seconds or longer. Values were sampled every 10 seconds within 24 hours after birth until at least 36 weeks' postmenstrual age. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of death after 36 weeks' postmenstrual age, motor impairment, cognitive or language delay, severe hearing loss, or bilateral blindness at 18 months' corrected age. Secondary outcomes were motor impairment, cognitive or language delay, and severe retinopathy of prematurity. RESULTS: Downloaded saturation and pulse rate data were available for a median of 68.3 days (interquartile range, 56.8-86.0 days). Mean percentages of recorded time with hypoxemia for the least and most affected 10% of infants were 0.4% and 13.5%, respectively. Corresponding values for bradycardia were 0.1% and 0.3%. The primary outcome was ascertained for 972 infants and present in 414 (42.6%). Hypoxemic episodes were associated with an estimated increased risk of late death or disability at 18 months of 56.5% in the highest decile of hypoxemic exposure vs 36.9% in the lowest decile (modeled relative risk, 1.53; 95% CI, 1.21-1.94). This association was significant only for prolonged hypoxemic episodes lasting at least 1 minute (relative risk, 1.66; 95% CI, 1.35-2.05 vs for shorter episodes, relative risk, 1.01; 95% CI, 0.77-1.32). Relative risks for all secondary outcomes were similarly increased after prolonged hypoxemia. Bradycardia did not alter the prognostic value of hypoxemia. CONCLUSIONS AND RELEVANCE: Among extremely preterm infants who survived to 36 weeks' postmenstrual age, prolonged hypoxemic episodes during the first 2 to 3 months after birth were associated with adverse 18-month outcomes. If confirmed in future studies, further research on the prevention of such episodes is needed.

Impact of study oximeter masking algorithm on titration of oxygen therapy in the Canadian oxygen trial.

OBJECTIVE: To compare oxygen saturations as displayed to caregivers on offset pulse oximeters in the 2 groups of the Canadian Oxygen Trial. STUDY DESIGN: In 5 double-blind randomized trials of oxygen saturation targeting, displayed saturations between 88% and 92% were offset by 3% above or below the true values but returned to true values below 84% and above 96%. During the transition, displayed values remained static at 96% in the lower and at 84% in the higher target group during a 3% change in true saturations. In contrast, displayed values changed rapidly from 88% to 84% in the lower and from 92% to 96% in the higher target group during a 1% change in true saturations. We plotted the distributions of median displayed saturations on days with >12 hours of supplemental oxygen in 1075 Canadian Oxygen Trial participants to reconstruct what caregivers observed at the bedside. RESULTS: The oximeter masking algorithm was associated with an increase in both stability and instability of displayed saturations that occurred during the transition between offset and true displayed values at opposite ends of the 2 target ranges. Caregivers maintained saturations at lower displayed values in the higher than in the lower target group. This differential management reduced the separation between the median true saturations in the 2 groups by approximately 3.5%. CONCLUSIONS: The design of the oximeter masking algorithm may have contributed to the smaller-than-expected separation between true saturations in the 2 study groups of recent saturation targeting trials in extremely preterm infants.

Red blood cell transfusion in newborn infants.

Red blood cell transfusion is an important and frequent component of neonatal intensive care. The present position statement addresses the methods and indications for red blood cell transfusion of the newborn, based on a review of the current literature. The most frequent indications for blood transfusion in the newborn are the acute treatment of perinatal hemorrhagic shock and the recurrent correction of anemia of prematurity. Perinatal hemorrhagic shock requires immediate treatment with large quantities of red blood cells; the effects of massive transfusion on other blood components must be considered. Some guidelines are now available from clinical trials investigating transfusion in anemia of prematurity; however, considerable uncertainty remains. There is weak evidence that cognitive impairment may be more severe at follow-up in extremely low birth weight infants transfused at lower hemoglobin thresholds; therefore, these thresholds should be maintained by transfusion therapy. Although the risks of transfusion have declined considerably in recent years, they can be minimized further by carefully restricting neonatal blood sampling.

La transfusion de culot globulaire est un élément important et fréquent des soins intensifs néonatals. Le présent document de principes traite des méthodes et des indications pour transfuser des culots globulaires au nouveau-né, d'après une analyse bibliographique. Les principales indications de transfusion sanguine au nouveau-né sont le traitement aigu du choc hémorragique périnatal et la correction récurrente de l'anémie de la prématurité. Le choc hémorragique périnatal exige l'administration immédiate de fortes quantités de culots globulaires, mais il faut tenir compte des effets d'une transfusion massive sur d'autres composants sanguins. Grâce à des essais cliniques sur les transfusions en cas d'anémie de la prématurité, il est désormais possible de compter sur des lignes directrices, même s'il reste beaucoup d'incertitude. D'après des données dont la qualité de preuves est faible, l'atteinte cognitive pourrait être plus grave au suivi chez les nouveau-nés d'extrême petit poids à la naissance qui sont transfusés à des seuils d'hémoglobine bas. Il faut donc maintenir ces seuils par thérapie transfusionnelle. Même si les risques de transfusion ont diminué considérablement ces dernières années, on peut les réduire encore davantage en limitant soigneusement les ponctions capillaires néonatales.

Effects of targeting higher vs lower arterial oxygen saturations on death or disability in extremely preterm infants: a randomized clinical trial.

IMPORTANCE: The goal of oxygen therapy is to deliver sufficient oxygen to the tissues while minimizing oxygen toxicity and oxidative stress. It remains uncertain what values of arterial oxygen saturations achieve this balance in preterm infants. OBJECTIVE: To compare the effects of targeting lower or higher arterial oxygen saturations on the rate of death or disability in extremely preterm infants. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind trial in 25 hospitals in Canada, the United States, Argentina, Finland, Germany, and Israel in which 1201 infants with gestational ages of 23 weeks 0 days through 27 weeks 6 days were enrolled within 24 hours after birth between December 2006 and August 2010. Follow-up assessments began in October 2008 and ended in August 2012. INTERVENTIONS: Study participants were monitored until postmenstrual ages of 36 to 40 weeks with pulse oximeters that displayed saturations of either 3% above or below the true values. Caregivers adjusted the concentration of oxygen to achieve saturations between 88% and 92%, which produced 2 treatment groups with true target saturations of 85% to 89% (n = 602) or 91% to 95% (n = 599). Alarms were triggered when displayed saturations decreased to 86% or increased to 94%. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of death, gross motor disability, cognitive or language delay, severe hearing loss, or bilateral blindness at a corrected age of 18 months. Secondary outcomes included retinopathy of prematurity and brain injury. RESULTS: Of the 578 infants with adequate data for the primary outcome who were assigned to the lower target range, 298 (51.6%) died or survived with disability compared with 283 of the 569 infants (49.7%) assigned to the higher target range (odds ratio adjusted for center, 1.08; 95% CI, 0.85 to 1.37; P = .52). The rates of death were 16.6% for those in the 85% to 89% group and 15.3% for those in the 91% to 95% group (adjusted odds ratio, 1.11; 95% CI, 0.80 to 1.54; P = .54). Targeting lower saturations reduced the postmenstrual age at last use of oxygen therapy (adjusted mean difference, -0.8 weeks; 95% CI, -1.5 to -0.1; P = .03) but did not alter any other outcomes. CONCLUSION AND RELEVANCE: In extremely preterm infants, targeting oxygen saturations of 85% to 89% compared with 91% to 95% had no significant effect on the rate of death or disability at 18 months. These results may help determine the optimal target oxygen saturation. TRIAL REGISTRATIONS: ISRCTN Identifier: 62491227; ClinicalTrials.gov Identifier: NCT00637169.

Transfusion-related acute lung injury in the Canadian paediatric population.

BACKGROUND: The incidence of transfusion-related acute lung injury (TRALI) in adults is approximately one per 5000 transfusions. The Canadian Paediatric Surveillance Program undertook the present study to determine the incidence of TRALI in the paediatric population and to describe the characteristics and outcomes of children with TRALI. METHODS: The present surveillance study was conducted over a three-year period. RESULTS: Four TRALI cases were reported, yielding an incidence rate of 1.8 per 100,000 transfusions. The degree of severity varied: in two patients, only supplemental oxygen was necessary, while the other two required mechanical ventilation. CONCLUSION: TRALI was reported much less often in the present study compared with adult studies; therefore, it needs to be determined whether TRALI occurs less frequently in children, or alternatively, whether TRALI is recognized less often in children. The possibility that neonates who undergo cardiac surgery are at greater risk of TRALI than other patients should be addressed in future studies.

HISTORIQUE: L'incidence de syndrome respiratoire aigu post transfusionnel (TRALI) est d'environ un cas sur 5 000 transfusions chez les adultes. Le Programme canadien de surveillance pédiatrique (PCSP) a entrepris cette étude pour déterminer l'incidence de TRALI dans la population pédiatrique et pour décrire les caractéristiques et le sort des enfants qui ont un TRALI. MÉTHODOLOGIE: Les chercheurs ont mené l'étude de surveillance pendant trois ans. RÉSULTATS: Quatre cas de TRALI ont été signalés, pour une incidence de 1,8 cas sur 100 000 transfusions. Le degré de gravité variait : deux patients n'ont eu besoin que d'oxygène d'appoint, tandis que les deux autres ont eu besoin d'une ventilation mécanique. CONCLUSION: Dans le cadre de cette étude, le TRALI était beaucoup moins signalé que dans les études auprès d'adultes. Il faut donc déterminer si le TRALI est moins fréquent ou s'il est moins dépisté chez les enfants. Lors de futures études, il faudra évaluer la possibilité que les nouveau-nés qui subissent une chirurgie cardiaque soient plus vulnérables au TRALI que les autres patients.

Low versus high haemoglobin concentration threshold for blood transfusion for preventing morbidity and mortality in very low birth weight infants.

BACKGROUND: Infants of very low birth weight often receive multiple transfusions of red blood cells, usually in response to predetermined haemoglobin or haematocrit thresholds. In the absence of better indices, haemoglobin levels are imperfect but necessary guides to the need for transfusion. Chronic anaemia in premature infants may, if severe, cause apnoea, poor neurodevelopmental outcomes or poor weight gain.On the other hand, red blood cell transfusion may result in transmission of infections, circulatory or iron overload, or dysfunctional oxygen carriage and delivery. OBJECTIVES: To determine if erythrocyte transfusion administered to maintain low as compared to high haemoglobin thresholds reduces mortality or morbidity in very low birth weight infants enrolled within three days of birth. SEARCH METHODS: Two review authors independently searched the Cochrane Central Register of Controlled Trials (The Cochrane Library) , MEDLINE,EMBASE, and conference proceedings through June 2010. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) comparing the effects of early versus late, or restrictive versus liberal erythrocyte transfusion regimes in low birth weight infants applied within three days of birth, with mortality or major morbidity as outcomes.

The effect of umbilical cord milking on cerebral blood flow in very preterm infants: a randomized controlled study.

OBJECTIVE: To compare the effect of umbilical cord milking (UCM) vs. early cord clamping (ECC) on cerebral blood flow (CBF). METHOD: Preterm infants <31 weeks' gestation were randomized to receive UCM or ECC at birth. Blood flow velocities and resistive & pulsatility indices of middle and anterior cerebral arteries were measured at 4-6 and 10-12 h after birth as an estimate of CBF. RESULTS: Randomization allocated 37 infants to UCM and 36 to ECC. Maternal and antenatal variables were similar. There were no significant differences between groups in middle or anterior CBF velocities and resistive indices at either study time point. CBF variables were not correlated with mean blood pressure, systemic blood flow, or intraventricular hemorrhage. CONCLUSIONS: In very preterm infants, UCM compared with ECC was not shown to change CBF indices during the first 12 h of age or correlate with other hemodynamic measures or with intraventricular hemorrhage. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01487187.

Oxygen saturation target ranges and alarm settings in the NICU: What have we learnt from the neonatal oxygenation prospective meta-analysis (NeOProM)?

The Neonatal Oxygenation Prospective Meta-analysis combined the individual participant data of 4965 extremely preterm infants. They had been randomly assigned in 5 trials to arterial oxygen saturations of 85%-89% or 91%-95% using modified oximeters to mask the treatment allocation. The primary outcome of death or disability did not differ significantly between the groups. Assignment to the higher target range reduced the risks of death and severe necrotizing enterocolitis but increased the risk of treated retinopathy. Trade-offs between the benefits and risks of higher or lower saturation targets should be informed by the local patient risks and institutional rates for outcomes that may be affected by a policy change. Features of the oximeter masking algorithm introduced unanticipated artifacts into the saturation display that are not seen in routine care. NeOProM provides little guidance on where to set the oximeter alarms and how to respond to them.