Resuscitation 95 (2015) 249–263 Contents lists available at ScienceDirect Resuscitation journal homepage: www.elsevier.com/locate/resuscitation European Resuscitation Council Guidelines for Resuscitation 2015 Section 7. Resuscitation and support of transition of babies at birth Jonathan Wylliea,∗ , Jos Bruinenbergb , Charles Christoph Roehrd,e , Mario Rüdigerf , Daniele Trevisanutoc , Berndt Urlesbergerg a Department of Neonatology, The James Cook University Hospital, Middlesbrough, UK b Department of Paediatrics, Sint Elisabeth Hospital, Tilburg, The Netherlands c Department of Women and Children’s’ Health, Padua University, Azienda Ospediliera di Padova, Padua, Italy d Department of Neonatology, Charité Universitätsmedizin, Berlin, Berlin, Germany e Newborn Services, John Radcliffe Hospital, Oxford University Hospitals, Oxford, UK f Department of Neonatology, Medizinische Fakultät Carl Gustav Carus, TU Dresden, Germany g Division of Neonatology, Medical University Graz, Graz, Austria Introduction The following guidelines for resuscitation at birth have been developed during the process that culminated in the 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations (CoSTR, 2015).1,2 They are an extension of the guidelines already published by the ERC3 and take into account recommendations made by other national and international organisations and previously evaluated evidence.4 Summary of changes since 2010 guidelines The following are the main changes that have been made to the guidelines for resuscitation at birth in 2015: • Support of transition: Recognising the unique situation of the baby at birth, who rarely requires ‘resuscitation’ but sometimes needs medical help during the process of postnatal transition. The term ‘support of transition’ has been introduced to better distinguish between interventions that are needed to restore vital organ functions (resuscitation) or to support transition. • Cord clamping: For uncompromised babies, a delay in cord clamping of at least 1 min from the complete delivery of the infant, is now recommended for term and preterm babies. As yet there is insufficient evidence to recommend an appropriate time for clamping the cord in babies who require resuscitation at birth. • Temperature: The temperature of newly born non-asphyxiated infants should be maintained between 36.5 ◦C and 37.5 ◦C after birth. The importance of achieving this has been highlighted and ∗ Corresponding author. E-mail address: jonathan.wyllie@stees.nhs.uk (J. Wyllie). reinforced because of the strong association with mortality and morbidity. The admission temperature should be recorded as a predictor of outcomes as well as a quality indicator. • Maintenance of temperature: At <32 weeks gestation, a combination of interventions may be required to maintain the temperature between 36.5 ◦C and 37.5 ◦C after delivery through admission and stabilisation. These may include warmed humidified respiratory gases, increased room temperature plus plastic wrapping of body and head, plus thermal mattress or a thermal mattress alone, all of which have been effective in reducing hypothermia. • Optimal assessment of heart rate: It is suggested in babies requiring resuscitation that the ECG can be used to provide a rapid and accurate estimation of heart rate. • Meconium: Tracheal intubation should not be routine in the presence of meconium and should only be performed for suspected tracheal obstruction. The emphasis should be on initiating ventilation within the first minute of life in non-breathing or ineffectively breathing infants and this should not be delayed. • Air/Oxygen: Ventilatory support of term infants should start with air. For preterm infants, either air or a low concentration of oxygen (up to 30%) should be used initially. If, despite effective ventilation, oxygenation (ideally guided by oximetry) remains unacceptable, use of a higher concentration of oxygen should be considered. • Continuous Positive Airways Pressure (CPAP): Initial respiratory support of spontaneously breathing preterm infants with respiratory distress may be provided by CPAP rather than intu- bation. The guidelines that follow do not define the only way that resuscitation at birth should be achieved; they merely represent a widely accepted view of how resuscitation at birth can be carried out both safely and effectively (Fig. 7.1). http://dx.doi.org/10.1016/j.resuscitation.2015.07.029 0300-9572/© 2015 European Resuscitation Council. Published by Elsevier Ireland Ltd. All rights reserved. 250 J. Wyllie et al. / Resuscitation 95 (2015) 249–263 (Antenatal counselling) Team briefing and equipment check Dry the baby Maintain normal temperature Start the clock or note the time If gasping or not breathing: Open the airway Give 5 inflation breaths Consider SpO2 ± ECG monitoring Reassess heart rate every 30 seconds If heart rate is not detectable or very slow (< 60 min-1 ) consider venous access and drugs If chest not moving: Recheck head position Consider 2-person airway control and other airway manoeuvres Repeat inflation breaths SpO2 monitoring ± ECG monitoring Look for a response Assess (tone), breathing and heart rate Discuss with parents and debrief team Re-assess If no increase in heart rate look for chest movement If no increase in heart rate look for chest movement When the chest is moving: If heart rate is not detectable or very slow (< 60 min-1 ) Start chest compressions Coordinate compressions with PPV (3:1) Birth Acceptable pre-ductal SpO2 2 min 60% 3 min 70% 4 min 80% 5 min 85% 10 min 90% 60 s Increaseoxygen (Guidedbyoximetryifavailable) At All Times Ask: Do You Need Help? MaintainTemperature Fig. 7.1. Newborn life support algorithm. SpO2: transcutaneous pulse oximetry, ECG: electrocardiograph, PPV: positive pressure ventilation. J. Wyllie et al. / Resuscitation 95 (2015) 249–263 251 Preparation The fetal-to-neonatal transition, which occurs at the time of birth, requires anatomic and physiological adjustments to achieve the conversion from placental gas exchange with intra-uterine lungs filled with fluid, to pulmonary respiration with aerated lungs. The absorption of lung fluid, the aeration of the lungs, the initiation of air breathing, and cessation of the placental circulation bring about this transition. A minority of infants require resuscitation at birth, but a few more have problems with this perinatal transition, which, if no support is given, might subsequently result in a need for resuscitation. Of those needing any help, the overwhelming majority will require only assisted lung aeration. A tiny minority may need a brief period of chest compressions in addition to lung aeration. In a retrospective study, approximately 85% of babies born at term initiated spontaneous respirations within 10 to 30 s of birth; an additional 10% responded during drying and stimulation, approximately 3% initiated respirations following positive pressure ventilation, 2% were intubated to support respiratory function and 0.1% received chest compressions and/or adrenaline.5–7 However, of 97,648 babies born in Sweden in one year, only 10 per 1000 (1%) babies of 2.5 kg or more appeared to need any resuscitation at delivery.8 Most of those, 8 per 1000, responded to mask inflation of the lungs and only 2 per 1000 appeared to need intubation. The same study tried to assess the unexpected need for resuscitation at birth and found that for low risk babies, i.e. those born after 32 weeks gestation and following an apparently normal labour, about 2 per 1000 (0.2%) appeared to need resuscitation or help with transition at delivery. Of these, 90% responded to mask ventilation alone while the remaining 10% appeared not to respond to mask inflation and therefore were intubated at birth. There was almost no need for cardiac compres- sions. Resuscitation or support of transition is more likely to be needed by babies with intrapartum evidence of significant fetal compromise, babies delivering before 35 weeks gestation, babies delivering vaginally by the breech, maternal infection and multiple pregnancies.9 Furthermore, caesarean delivery is associated with an increased risk of problems with respiratory transition at birth requiring medical interventions especially for deliveries before 39 weeks gestation.10–13 However, elective caesarean delivery at term does not increase the risk of needing newborn resuscitation in the absence of other risk factors.14–17 Although it is sometimes possible to predict the need for resuscitation or stabilisation before a baby is born, this is not always the case. Any newborn may potentially develop problems during birth, therefore, personnel trained in newborn life support should be easily available for every delivery. In deliveries with a known increased risk of problems, specially trained personnel should be present with at least one person experienced in tracheal intubation. Should there be any need for intervention, the care of the baby should be their sole responsibility. Local guidelines indicating who should attend deliveries should be developed, based on current practice and clinical audit. Each institution should have a protocol in place for rapidly mobilising a team with competent resuscitation skills for any birth. Whenever there is sufficient time, the team attending the delivery should be briefed before delivery and clear role assignment should be defined. It is also important to prepare the family in cases where it is likely that resuscitation might be required. A structured educational programme, teaching the standards and skills required for resuscitation of the newborn is therefore essential for any institution or clinical area in which deliveries may occur. Continued experiential learning and practice is necessary to maintain skills. Planned home deliveries Recommendations as to who should attend a planned home delivery vary from country to country, but the decision to undergo a planned home delivery, once agreed with medical and midwifery staff, should not compromise the standard of initial assessment, stabilisation or resuscitation at birth. There will inevitably be some limitations to resuscitation of a newborn baby in the home, because of the distance from further assistance, and this must be made clear to the mother at the time plans for home delivery are made. Ideally, two trained professionals should be present at all home deliveries; one of these must be fully trained and experienced in providing mask ventilation and chest compressions in the newborn. Equipment and environment Unlike adult cardiopulmonary resuscitation (CPR), resuscitation at birth is often a predictable event. It is therefore possible to prepare the environment and the equipment before delivery of the baby. Resuscitation should take place in a warm, well-lit, draught free area with a flat resuscitation surface placed below a radiant heater (if in hospital), with other resuscitation equipment immediately available. All equipment must be regularly checked and tested. When a birth takes place in a non-designated delivery area, the recommended minimum set of equipment includes a device for safe assisted lung aeration and subsequent ventilation of an appropriate size for the newborn, warm dry towels and blankets, a sterile instrument for cutting and clamping the umbilical cord and clean gloves for the attendant and assistants. Unexpected deliveries outside hospital are most likely to involve emergency services that should plan for such events. Timing of clamping the umbilical cord Cine-radiographic studies of babies taking their first breath at delivery showed that those whose cords were clamped prior to this had an immediate decrease in the size of the heart during the subsequent three or four cardiac cycles. The heart then increased in size to almost the same size as the fetal heart. The initial decrease in size could be interpreted as the significantly increased pulmonary blood flow following the decrease in pulmonary vascular resistance upon lung aeration. The subsequent increase in size would, as a consequence, be caused by the blood returning to the heart from the lung.18 Brady et al drew attention to the occurrence of a bradycardia apparently induced by clamping the cord before the first breath and noted that this did not occur in babies where clamping occurred after breathing was established.19 Experimental evidence from similarly treated lambs suggest the same holds true for premature newborn.20 Studies of delayed clamping have shown an improvement in iron status and a number of other haematological indices over the next 3–6 months and a reduced need for transfusion in preterm infants.21,22 They have also suggested greater use of phototherapy for jaundice in the delayed group but this was not found in a randomised controlled trial.21 A systematic review on delayed cord clamping and cord milking in preterm infants found improved stability in the immediate postnatal period, including higher mean blood pressure and haemoglobin on admission, compared to controls.23 There were also fewer blood transfusions in the ensuing weeks.23 Some studies have suggested a reduced incidence of intraventricular haemorrhage and periventricular leukomalacia22,24,25 as well as of late-onset sepsis.24 252 J. Wyllie et al. / Resuscitation 95 (2015) 249–263 No human studies have yet addressed the effect of delaying cord clamping on babies apparently needing resuscitation at birth because such babies have been excluded from previous studies. Delaying umbilical cord clamping for at least 1 min is recommended for newborn infants not requiring resuscitation. A similar delay should be applied to preterm babies not requiring immediate resuscitation after birth. Until more evidence is available, infants who are not breathing or crying may require the umbilical cord to be clamped, so that resuscitation measures can commence promptly. Umbilical cord milking may prove an alternative in these infants although there is currently not enough evidence available to recommended this as a routine measure.1,2 Umbilical cord milking produces improved short term haematological outcomes, admission temperature and urine output when compared to delayed cord clamping (>30 s) in babies born by caesarean section, although these differences were not observed in infants born vaginally.26 Temperature control Naked, wet, newborn babies cannot maintain their body temperature in a room that feels comfortably warm for adults. Compromised babies are particularly vulnerable.27 Exposure of the newborn to cold stress will lower arterial oxygen tension28 and increase metabolic acidosis.29 The association between hypothermia and mortality has been known for more than a century,30 and the admission temperature of newborn non-asphyxiated infants is a strong predictor of mortality at all gestations and in all settings.31–65 Preterm infants are especially vulnerable and hypothermia is also associated with serious morbidities such as intraventricular haemorrhage35,42,55,66–69 need for respiratory support31,35,37,66,70–74 hypoglycaemia31,49,60,74–79 and in some studies late onset sepsis.49 The temperature of newly born non-asphyxiated infants should be maintained between 36.5 ◦C and 37.5 ◦C after birth. For each 1 ◦C decrease in admission temperature below this range there is an associated increase in mortality by 28%.1,2,49 The admission temperature should be recorded as a predictor of outcomes as well as a quality indicator. Prevent heat loss: • Protect the baby from draughts.80 Make certain windows closed and air-conditioning appropriately programmed.52 • Dry the term baby immediately after delivery. Cover the head and body of the baby, apart from the face, with a warm and dry towel to prevent further heat loss. Alternatively, place the baby skin to skin with mother and cover both with a towel. • Keep the delivery room warm at 23–25 ◦C.1,2,48,80 For babies less than 28 weeks gestation the delivery room temperature should be >25 ◦C.27,48,79,81 • If the baby needs support in transition or resuscitation then place the baby on a warm surface under a preheated radiant warmer. • All babies less than 32 weeks gestation should have the head and body of the baby (apart from the face) covered with polyethylene wrapping, without drying the baby beforehand, and also placed under a radiant heater.73,77,82,83 • In addition, babies <32 weeks gestation, may require a combination of further interventions to maintain the temperature between 36.5 ◦C and 37.5 ◦C after delivery through admission and stabilisation. These may include warmed humidified respiratory gases,84,85 increased room temperature plus cap plus thermal mattress 70,72,86,87 or thermal mattress alone,88–92 which have all been effective in reducing hypothermia. • Babies born unexpectedly outside a normal delivery environment may benefit from placement in a food grade plastic bag after drying and then swaddling.93,94 Alternatively, well newborns >30 weeks gestation may be dried and nursed with skin to skin contact or kangaroo mother care to maintain their temperature whilst they are transferred.95–101 They should be covered and protected from draughts. Whilst maintenance of a baby’s temperature is important, this should be monitored in order to avoid hyperthermia (>38.0 ◦C). Infants born to febrile mothers have a higher incidence of perinatal respiratory depression, neonatal seizures, early mortality and cerebral palsy.102,103 Animal studies indicate that hyperthermia during or following ischaemia is associated with a progression of cerebral injury.104,105 Initial assessment The Apgar score was not designed to be assembled and ascribed in order to then identify babies in need of resuscitation.106,107 However, individual components of the score, namely respiratory rate, heart rate and tone, if assessed rapidly, can identify babies needing resuscitation, (and Virginia Apgar herself found that heart rate was the most important predictor of immediate outcome).106 Furthermore, repeated assessment particularly of heart rate and, to a lesser extent breathing, can indicate whether the baby is responding or whether further efforts are needed. Breathing Check whether the baby is breathing. If so, evaluate the rate, depth and symmetry of breathing together with any evidence of an abnormal breathing pattern such as gasping or grunting. Heart rate Immediately after birth the heart rate is assessed to evaluate the condition of the baby and subsequently is the most sensitive indicator of a successful response to interventions. Heart rate is initially most rapidly and accurately assessed by listening to the apex beat with a stethoscope108 or by using an electrocardiograph.109–112 Feeling the pulse in the base of the umbilical cord is often effective but can be misleading because cord pulsation is only reliable if found to be more than 100 beats per minute (bpm)108 and clinical assessment may underestimate the heart rate.108,109,113 For babies requiring resuscitation and/or continued respiratory support, a modern pulse oximeter can give an accurate heart rate.111 Several studies have demonstrated that ECG is faster than pulse oximetry and more reliable, especially in the first 2 min after birth;110–115 however, the use of ECG does not replace the need to use pulse oximetry to assess the newborn baby’s oxygenation. Colour Colour is a poor means of judging oxygenation,116 which is better assessed using pulse oximetry if possible. A healthy baby is born blue but starts to become pink within 30 s of the onset of effective breathing. Peripheral cyanosis is common and does not, by itself, indicate hypoxaemia. Persistent pallor despite ventilation may indicate significant acidosis or rarely hypovolaemia. Although colour is a poor method of judging oxygenation, it should not be ignored: if a baby appears blue, check preductal oxygenation with a pulse oximeter. Tone A very floppy baby is likely to be unconscious and will need ventilatory support. J. Wyllie et al. / Resuscitation 95 (2015) 249–263 253 Tactile stimulation Drying the baby usually produces enough stimulation to induce effective breathing. Avoid more vigorous methods of stimulation. If the baby fails to establish spontaneous and effective breaths following a brief period of stimulation, further support will be required. Classification according to initial assessment On the basis of the initial assessment, the baby can be placed into one of three groups: (1) Vigorous breathing or crying. Good tone. Heart rate higher than 100 min−1 . There is no need for immediate clamping of the cord. This baby requires no intervention other than drying, wrapping in a warm towel and, where appropriate, handing to the mother. The baby will remain warm through skin-to-skin contact with mother under a cover, and may be put to the breast at this stage. It remains important to ensure the baby’s temperature is maintained. (2) Breathing inadequately or apnoeic. Normal or reduced tone. Heart rate less than 100 min−1 . Dry and wrap. This baby will usually improve with mask inflation but if this does not increase the heart rate adequately, may rarely also require ventilations. (3) Breathing inadequately or apnoeic. Floppy. Low or undetectable heart rate. Often pale suggesting poor perfusion. Dry and wrap. This baby will then require immediate airway control, lung inflation and ventilation. Once this has been successfully accomplished the baby may also need chest compressions, and perhaps drugs. Preterm babies may be breathing and showing signs of respiratory distress in which case they should be supported initially with CPAP. There remains a very rare group of babies who, though breathing with a good heart rate, remain hypoxaemic. This group includes a range of possible diagnoses such as cyanotic congenital heart disease, congenital pneumonia, pneumothorax, diaphragmatic hernia or surfactant deficiency. Newborn life support Commence newborn life support if initial assessment shows that the baby has failed to establish adequate regular normal breathing, or has a heart rate of less than 100 min−1 (Fig. 7.1). Opening the airway and aerating the lungs is usually all that is necessary. Furthermore, more complex interventions will be futile unless these two first steps have been successfully completed. Airway Place the baby on his or her back with the head in a neutral position (Fig. 7.2). A 2 cm thickness of the blanket or towel placed under the baby’s shoulder may be helpful in maintaining proper head position. In floppy babies application of jaw thrust or the use of an appropriately sized oropharyngeal airway may be essential in opening the airway. The supine position for airway management is traditional but side-lying has also been used for assessment and routine delivery room management of term newborns but not for resuscitation.117 Fig. 7.2. Newborn with head in neutral position. There is no need to remove lung fluid from the oropharynx routinely.118 Suction is needed only if the airway is obstructed. Obstruction may be caused by particulate meconium but can also be caused by blood clots, thick tenacious mucus or vernix even in deliveries where meconium staining is not present. However, aggressive pharyngeal suction can delay the onset of spontaneous breathing and cause laryngeal spasm and vagal bradycardia.119–121 Meconium For over 30 years it was hoped that clearing meconium from the airway of babies at birth would reduce the incidence and severity of meconium aspiration syndrome (MAS). However, studies supporting this view were based on a comparison of suctioning on the outcome of a group of babies with the outcome of historical controls.122,123 Furthermore other studies failed to find any evidence of benefit from this practice.124,125 Lightly meconium stained liquor is common and does not, in general, give rise to much difficulty with transition. The much less common finding of very thick meconium stained liquor at birth is an indicator of perinatal distress and should alert to the potential need for resuscitation. Two multi-centre randomised controlled trials showed that routine elective intubation and tracheal suctioning of these infants, if vigorous at birth, did not reduce MAS 126 and that suctioning the nose and mouth of such babies on the perineum and before delivery of the shoulders (intrapartum suctioning) was ineffective.127 Hence intrapartum suctioning and routine intubation and suctioning of vigorous infants born through meconium stained liquor are not recommended. A small RCT has recently demonstrated no difference in the incidence of MAS between patients receiving tracheal intubation followed by suctioning and those not intubated.128 The presence of thick, viscous meconium in a non-vigorous baby is the only indication for initially considering visualising the oropharynx and suctioning material, which might obstruct the airway. Tracheal intubation should not be routine in the presence of meconium and should only be performed for suspected tracheal obstruction.128–132 The emphasis should be on initiating ventilation within the first minute of life in non-breathing or ineffectively breathing infants and this should not be delayed. If suctioning is attempted use a 12–14 FG suction catheter, or a paediatric Yankauer sucker, connected to a suction source not exceeding −150 mmHg.133 The routine administration of surfactant or bronchial lavage with either saline or surfactant is not recommended.134,135 Initial breaths and assisted ventilation After initial steps at birth, if breathing efforts are absent or inadequate, lung aeration is the priority and must not be delayed (Fig. 7.3). In term babies, respiratory support should start with air.136 The primary measure of adequate initial lung inflation is a 254 J. Wyllie et al. / Resuscitation 95 (2015) 249–263 Fig. 7.3. Mask ventilation of newborn. prompt improvement in heart rate. If the heart rate is not improving assess the chest wall movement. In term infants, spontaneous or assisted initial inflations create a functional residual capacity (FRC).137–141 The optimum pressure, inflation time and flow required to establish an effective FRC has not been determined. For the first five positive pressure inflations maintain the initial inflation pressure for 2–3 s. This will usually help lung expansion.137,142 The pressure required to aerate the fluid filled lungs of newborn babies requiring resuscitation is 15–30 cm H2O (1.5–2.9 kPa) with a mean of 20 cm H2O.137,141,142 For term babies use an inflation pressure of 30 cm H2O and 20–25 cm H2O in preterm babies.143,144 Efficacy of the intervention can be estimated by a prompt increase in heart rate or observing the chest rise. If this is not obtained it is likely that repositioning of the airway or mask will be required and, rarely, higher inspiratory pressures may be needed. Most babies needing respiratory support at birth will respond with a rapid increase in heart rate within 30 s of lung inflation. If the heart rate increases but the baby is not breathing adequately, ventilate at a rate of about 30 breaths min−1 allowing approximately 1 s for each inflation, until there is adequate spontaneous breathing. Adequate passive ventilation is usually indicated by either a rapidly increasing heart rate or a heart rate that is maintained faster than 100 beats min−1. If the baby does not respond in this way the most likely cause is inadequate airway control or inadequate ventilation. Look for passive chest movement in time with inflation efforts; if these are present then lung aeration has been achieved. If these are absent then airway control and lung aeration has not been confirmed. Mask leak, inappropriate airway position and airway obstruction, are all possible reasons, which may need correction.145–149 In this case, consider repositioning the mask to correct for leakage and/or reposition the baby’s head to correct for airway obstruction.145 Alternatively using a two person approach to mask ventilation reduces mask leak in term and preterm infants.146,147 Without adequate lung aeration, chest compressions will be ineffective; therefore, confirm lung aeration and ventilation before progressing to circulatory support. Some practitioners will ensure airway control by tracheal intubation, but this requires training and experience. If this skill is not available and the heart rate is decreasing, re-evaluate the airway position and deliver inflation breaths while summoning a colleague with intubation skills. Continue ventilatory support until the baby has established normal regular breathing. Fig. 7.4. Oxygen saturations (3rd, 10th, 25th, 50th, 75th, 90th, and 97th SpO2 percentiles) in healthy infants at birth without medical intervention. Reproduced with permission from. 157 Sustained inflations (SI) > 5 s Several animal studies have suggested that a longer SI may be beneficial for establishing functional residual capacity at birth during transition from a fluid-filled to air-filled lung.150,151 Review of the literature in 2015 disclosed three RCTs152–154 and two cohort studies,144,155 which demonstrated that initial SI reduced the need for mechanical ventilation. However, no benefit was found for reduction of mortality, bronchopulmonary dysplasia, or air leak. One cohort study144 suggested that the need for intubation was less following SI. It was the consensus of the COSTR reviewers that there was inadequate study of the safety, details of the most appropriate length and pressure of inflation, and long-term effects, to suggest routine application of SI of greater than 5 s duration to the transitioning newborn.1,2 Sustained inflations >5 s should only be considered in individual clinical circumstances or in a research setting. Air/Oxygen Term babies. In term infants receiving respiratory support at birth with positive pressure ventilation (PPV), it is best to begin with air (21%) as opposed to 100% oxygen. If, despite effective ventilation, there is no increase in heart rate or oxygenation (guided by oximetry wherever possible) remains unacceptable, use a higher concentration of oxygen to achieve an adequate preductal oxygen saturation.156,157 High concentrations of oxygen are associated with an increased mortality and delay in time of onset of spontaneous breathing,158 therefore, if increased oxygen concentrations are used they should be weaned as soon as possible.136,159 Preterm babies. Resuscitation of preterm infants less than 35 weeks gestation at birth should be initiated in air or low concentration oxygen (21–30%).1,2,136,160 The administered oxygen concentration should be titrated to achieve acceptable pre-ductal oxygen saturations approximating to the 25th percentile in healthy term babies immediately after birth (Fig. 7.4).156,157 In a meta-analysis of seven randomized trials comparing initiation of resuscitation with high (>65%) or low (21–30%) oxygen concentrations, the high concentration was not associated with any improvement in survival,159,161–166 bronchopulmonary dysplasia,159,162,164–166 intraventricular haemorrhage159,162,165,166 or retinopathy of prematurity.159,162,166 There was an increase in markers of oxidative stress.159 Pulse oximetry. Modern pulse oximetery, using neonatal probes, provides reliable readings of heart rate and transcutaneous oxygen saturation within 1–2 min of birth (Fig. 7.4).167,168 A reliable J. Wyllie et al. / Resuscitation 95 (2015) 249–263 255 pre-ductal reading can be obtained from >90% of normal term births, approximately 80% of those born preterm, and 80-90% of those apparently requiring resuscitation, within 2 min of birth.167 Uncompromised babies born at term at sea level have SpO2 ∼60% during labour,169 which increases to >90% by 10 min.156 The 25th percentile is approximately 40% at birth and increases to ∼80% at 10 min.157 Values are lower in those born by Caesarean delivery,170 those born at altitude171 and those managed with delayed cord clamping.172 Those born preterm may take longer to reach >90%.157 Pulse oximetry should be used to avoid excessive use of oxygen as well as to direct its judicious use (Figs. 7.1 and 7.4). Transcutaneous oxygen saturations above the acceptable levels should prompt weaning of any supplemental oxygen. Positive end expiratory pressure All term and preterm babies who remain apnoeic despite initial steps must receive positive pressure ventilation after initial lung inflation. It is suggested that positive end expiratory pressure (PEEP) of ∼5 cm H2O should be administered to preterm newborn babies receiving PPV.173 Animal studies show that preterm lungs are easily damaged by large-volume inflations immediately after birth174 and suggest that maintaining a PEEP immediately after birth may protect against lung damage175,176 although some evidence suggests no benefit.177 PEEP also improves lung aeration, compliance and gas exchange.178–180 Two human newborn RCTs demonstrated no improvement in mortality, need for resuscitation or bronchopulmonary dysplasia they were underpowered for these outcomes.181,182 However, one of the trials suggested that PEEP reduced the amount of supplementary oxygen required.182 Assisted ventilation devices Effective ventilation can be achieved with a flow-inflating, a self-inflating bag or with a T-piece mechanical device designed to regulate pressure.181–185 The blow-off valves of self-inflating bags are flow-dependent and pressures generated may exceed the value specified by the manufacturer if compressed vigorously.186,187 Target inflation pressures, tidal volumes and long inspiratory times are achieved more consistently in mechanical models when using T-piece devices than when using bags,187–190 although the clinical implications are not clear. More training is required to provide an appropriate pressure using flow-inflating bags compared with self-inflating bags.191 A self-inflating bag, a flow-inflating bag or a T-piece mechanical device, all designed to regulate pressure or limit pressure applied to the airway can be used to ventilate a newborn. However, self-inflating bags are the only devices, which can be used in the absence of compressed gas but cannot deliver continuous positive airway pressure (CPAP) and may not be able to achieve PEEP even with a PEEP valve in place189,192–195 Respiratory function monitors measuring inspiratory pressures and tidal volumes 196 and exhaled carbon dioxide monitors to assess ventilation 197,198 have been used but there is no evidence that they affect outcomes. Neither additional benefit above clinical assessment alone, nor risks attributed to their use have so far been identified. The use of exhaled CO2 detectors to assess ventilation with other interfaces (e.g., nasal airways, laryngeal masks) during PPV in the delivery room has not been reported. Face mask versus nasal prong A reported problem of using the facemask for newborn ventilation is mask leak caused by a failure of the seal between the mask and the face.145–148 To avoid this some institutions are using nasopharyngeal prongs to deliver respiratory support. Two randomised Table 1 Oral tracheal tube lengths by gestation. Gestation (weeks) ETT at lips (cm) 23–24 5·5 25–26 6·0 27–29 6·5 30–32 7·0 33–34 7·5 35–37 8·0 38–40 8·5 41–43 9·0 trials in preterm infants have compared the efficacy and did not find any difference between the methods.199,200 Laryngeal mask airway The laryngeal mask airway can be used in resuscitation of the newborn, particularly if facemask ventilation is unsuccessful or tracheal intubation is unsuccessful or not feasible. The LMA may be considered as an alternative to a facemask for positive pressure ventilation among newborns weighing more than 2000 g or delivered ≥34 weeks gestation.201 One recent unblinded RCT demonstrated that following training with one type of LMA, its use was associated with less tracheal intubation and neonatal unit admission in comparison to those receiving ventilation via a facemask.201 There is limited evidence, however, to evaluate its use for newborns weighing <2000 gram or delivered <34 weeks gestation. The laryngeal mask airway may be considered as an alternative to tracheal intubation as a secondary airway for resuscitation among newborns weighing more than 2000 g or delivered ≥34 weeks gestation.201–206 The LMA is recommended during resuscitation of term and preterm newborns ≥34 weeks gestation when tracheal intubation is unsuccessful or not feasible. The laryngeal mask airway has not been evaluated in the setting of meconium stained fluid, during chest compressions, or for the administration of emergency intra-tracheal medications. Tracheal tube placement Tracheal intubation may be considered at several points during neonatal resuscitation: • When suctioning the lower airways to remove a presumed tracheal blockage. • When, after correction of mask technique and/or the baby’s head position, bag-mask ventilation is ineffective or prolonged. • When chest compressions are performed. • Special circumstances (e.g., congenital diaphragmatic hernia or to give tracheal surfactant). The use and timing of tracheal intubation will depend on the skill and experience of the available resuscitators. Appropriate tube lengths based on gestation are shown in Table 1.207 It should be recognised that vocal cord guides, as marked on tracheal tubes by different manufacturers to aid correct placement, vary considerably.208 Tracheal tube placement must be assessed visually during intubation, and positioning confirmed. Following tracheal intubation and intermittent positive-pressure, a prompt increase in heart rate is a good indication that the tube is in the tracheobronchial tree. 209 Exhaled CO2 detection is effective for confirmation of tracheal tube placement in infants, including VLBW infants210–213 and neonatal studies suggest that it confirms tracheal intubation in neonates with a cardiac output more rapidly and more accurately than clinical assessment alone.212–214 Failure to detect exhaled CO2 strongly suggests oesophageal intubation210,212 but false negative readings have been reported during cardiac arrest 210 and in VLBW infants 256 J. Wyllie et al. / Resuscitation 95 (2015) 249–263 despite models suggesting efficacy.215 However, neonatal studies have excluded infants in need of extensive resuscitation. False positives may occur with colorimetric devices contaminated with adrenaline (epinephrine), surfactant and atropine.198 Poor or absent pulmonary blood flow or tracheal obstruction may prevent detection of exhaled CO2 despite correct tracheal tube placement. Tracheal tube placement is identified correctly in nearly all patients who are not in cardiac arrest211; however, in critically ill infants with poor cardiac output, inability to detect exhaled CO2 despite correct placement may lead to unnecessary extubation. Other clinical indicators of correct tracheal tube placement include evaluation of condensed humidified gas during exhalation and presence or absence of chest movement, but these have not been evaluated systematically in newborn babies. Detection of exhaled carbon dioxide in addition to clinical assessment is recommended as the most reliable method to confirm tracheal placement in neonates with spontaneous circulation.3,4 CPAP Initial respiratory support of all spontaneously breathing preterm infants with respiratory distress may be provided by CPAP, rather than intubation. Three RCTs enrolling 2358 infants born at <30 weeks gestation demonstrated that CPAP is beneficial when compared to initial tracheal ventilation and PPV in reducing the rate of intubation and duration of mechanical ventilation without any short term disadvantages.216–218 There are few data to guide the appropriate use of CPAP in term infants at birth and further clinical studies are required.219,220 Circulatory support Circulatory support with chest compressions is effective only if the lungs have first been successfully inflated. Give chest compressions if the heart rate is less than 60 beats min−1 despite adequate ventilation. As ventilation is the most effective and important intervention in newborn resuscitation, and may be compromised by compressions, it is vital to ensure that effective ventilation is occurring before commencing chest compressions. The most effective technique for providing chest compressions is with two thumbs over the lower third of the sternum with the fingers encircling the torso and supporting the back (Fig. 7.5).221–224 This technique generates higher blood pressures and coronary artery perfusion with less fatigue than the previously used twofinger technique.222–234 In a manikin study overlapping the thumbs on the sternum was more effective than positioning them adjacent but more likely to cause fatigue.235 The sternum is compressed to a depth of approximately one-third of the anterior-posterior diameter of the chest allowing the chest wall to return to its relaxed position between compressions.225,236–240 Use a 3:1 compression to ventilation ratio, aiming to achieve approximately 120 events per minute, i.e. approximately 90 compressions and 30 ventilations.241–246 There are theoretical advantages to allowing a relaxation phase that is very slightly longer than the compression phase.247 However, the quality of the compressions and breaths are probably more important than the rate. Compressions and ventilations should be coordinated to avoid simultaneous delivery.248 A 3:1 compression to ventilation ratio is used for resuscitation at birth where compromise of gas exchange is nearly always the primary cause of cardiovascular collapse, but rescuers may consider using higher ratios (e.g., 15:2) if the arrest is believed to be of cardiac origin. When resuscitation of a newborn baby has reached the stage of chest compressions, the steps of trying to achieve return of spontaneous circulation using effective ventilation with low Fig. 7.5. Ventilation and chest compression of newborn. concentration oxygen should have been attempted. Thus, it would appear sensible to try increasing the supplementary oxygen concentration towards 100%. There are no human studies to support this and animal studies demonstrate no advantage to 100% oxygen during CPR.249–255 Check the heart rate after about 30 s and periodically thereafter. Discontinue chest compressions when the spontaneous heart rate is faster than 60 beats min−1. Exhaled carbon dioxide monitoring and pulse oximetry have been reported to be useful in determining the return of spontaneous circulation256–260; however, current evidence does not support the use of any single feedback device in a clinical setting.1,2 Drugs Drugs are rarely indicated in resuscitation of the newly born infant. Bradycardia in the newborn infant is usually caused by inadequate lung inflation or profound hypoxia, and establishing adequate ventilation is the most important step to correct it. However, if the heart rate remains less than 60 beats min−1 despite adequate ventilation and chest compressions, it is reasonable to consider the use of drugs. These are best given via a centrally positioned umbilical venous catheter (Fig. 7.6). Adrenaline Despite the lack of human data it is reasonable to use adrenaline when adequate ventilation and chest compressions have failed to increase the heart rate above 60 beats min−1. If 2 umbilical arteries 1 umbilical vein LEGS HEAD Fig. 7.6. Newborn umbilical cord showing the arteries and veins. J. Wyllie et al. / Resuscitation 95 (2015) 249–263 257 adrenaline is used, an initial dose 10 micrograms kg−1 (0.1 ml kg−1 of 1:10,000 adrenaline) should be administered intravenously as soon as possible1,2,4 with subsequent intravenous doses of 10–30 micrograms kg−1 (0.1–0.3 ml kg−1 of 1:10,000 adrenaline) if required. The tracheal route is not recommended but if it is used, it is highly likely that doses of 50–100 micrograms kg−1 will be required.3,7,136,261–265 Neither the safety nor the efficacy of these higher tracheal doses has been studied. Do not give these high doses intravenously. Bicarbonate If effective spontaneous cardiac output is not restored despite adequate ventilation and adequate chest compressions, reversing intracardiac acidosis may improve myocardial function and achieve a spontaneous circulation. There are insufficient data to recommend routine use of bicarbonate in resuscitation of the newly born. The hyperosmolarity and carbon dioxide-generating properties of sodium bicarbonate may impair myocardial and cerebral function. Use of sodium bicarbonate is not recommended during brief CPR. If it is used during prolonged arrests unresponsive to other therapy, it should be given only after adequate ventilation and circulation is established with CPR. A dose of 1–2 mmol kg−1 may be given by slow intravenous injection after adequate ventilation and perfusion have been established. Fluids If there has been suspected blood loss or the infant appears to be in shock (pale, poor perfusion, weak pulse) and has not responded adequately to other resuscitative measures then consider giving fluid.266 This is a rare event. In the absence of suitable blood (i.e. irradiated and leucocyte-depleted group O Rh-negative blood), isotonic crystalloid rather than albumin is the solution of choice for restoring intravascular volume. Give a bolus of 10 ml kg−1 initially. If successful it may need to be repeated to maintain an improvement. When resuscitating preterm infants volume is rarely needed and has been associated with intraventricular and pulmonary haemorrhages when large volumes are infused rapidly. Withholding or discontinuing resuscitation Mortality and morbidity for newborns varies according to region and to availability of resources.267 Social science studies indicate that parents desire a larger role in decisions to resuscitate and to continue life support in severely compromised babies.268 Opinions vary amongst providers, parents and societies about the balance of benefits and disadvantages of using aggressive therapies in such babies.269,270 Local survival and outcome data are important in appropriate counselling of parents. A recent study suggests that the institutional approach at the border of viability affects the subsequent results in surviving infants.271 Discontinuing resuscitation Local and national committees will define recommendations for stopping resuscitation. If the heart rate of a newly born baby is not detectable and remains undetectable for 10 min, it may be appropriate to consider stopping resuscitation. The decision to continue resuscitation efforts when the heart rate has been undetectable for longer than 10 min is often complex and may be influenced by issues such as the presumed aetiology, the gestation of the baby, the potential reversibility of the situation, the availability of therapeutic hypothermia and the parents’ previous expressed feelings about acceptable risk of morbidity.267,272–276 The decision should be individualised. In cases where the heart rate is less than 60 min−1 at birth and does not improve after 10 or 15 min of continuous and apparently adequate resuscitative efforts, the choice is much less clear. In this situation there is insufficient evidence about outcome to enable firm guidance on whether to withhold or to continue resuscitation. Withholding resuscitation It is possible to identify conditions associated with high mortality and poor outcome, where withholding resuscitation may be considered reasonable, particularly when there has been the opportunity for discussion with parents.38,272,277–282 There is no evidence to support the prospective use of any particular delivery room prognostic score presently described, over gestational age assessment alone, in preterm infants <25 weeks gestation. A consistent and coordinated approach to individual cases by the obstetric and neonatal teams and the parents is an important goal.283 Withholding resuscitation and discontinuation of life-sustaining treatment during or following resuscitation are considered by many to be ethically equivalent and clinicians should not be hesitant to withdraw support when the possibility of functional survival is highly unlikely. The following guidelines must be interpreted according to current regional outcomes. • Where gestation, birth weight, and/or congenital anomalies are associated with almost certain early death, and unacceptably high morbidity is likely among the rare survivors, resuscitation is not indicated.38,277,284 Examples from the published literature include: extreme prematurity (gestational age less than 23 weeks and/or birth weight less than 400 g), and anomalies such as anencephaly and confirmed Trisomy 13 or 18. • Resuscitation is nearly always indicated in conditions associated with a high survival rate and acceptable morbidity. This will generally include babies with gestational age of 25 weeks or above (unless there is evidence of fetal compromise such as intrauterine infection or hypoxia-ischaemia) and those with most congenital malformations. • In conditions associated with uncertain prognosis, where there is borderline survival and a relatively high rate of morbidity, and where the anticipated burden to the child is high, parental desires regarding resuscitation should be supported.283 • When withdrawing or withholding resuscitation, care should be focused on the comfort and dignity of the baby and family. Communication with the parents It is important that the team caring for the newborn baby informs the parents of the baby’s progress. At delivery, adhere to the routine local plan and, if possible, hand the baby to the mother at the earliest opportunity. If resuscitation is required inform the parents of the procedures undertaken and why they were required. European guidelines are supportive of family presence during cardiopulmonary resuscitation.285 In recent years healthcare professionals are increasingly offering family members the opportunity to remain present during CPR and this is more likely if resuscitation takes place within the delivery room. Parents’ wishes to be present during resuscitation should be supported where possible.286 The members of the resuscitation team and family members, without coercion or pressure, make the decision about who should be present during resuscitation jointly. It is recommended to provide a healthcare professional whose sole responsibility is to care for the family member. Whilst this may not always be possible it should not mean the exclusion of the family member from the resuscitation. Finally, there should be an opportunity for the immediate relative to reflect, ask questions about details of the resuscitation and be informed about the support services available.286 258 J. Wyllie et al. / Resuscitation 95 (2015) 249–263 Decisions to discontinue resuscitation should ideally involve senior paediatric staff. Whenever possible, the decision to attempt resuscitation of an extremely preterm baby should be taken in close consultation with the parents and senior paediatric and obstetric staff. Where a difficulty has been foreseen, for example in the case of severe congenital malformation, discuss the options and prognosis with the parents, midwives, obstetricians and birth attendants before delivery.283 Record carefully all discussions and decisions in the mother’s notes prior to delivery and in the baby’s records after birth. Post-resuscitation care Babies who have required resuscitation may later deteriorate. Once adequate ventilation and circulation are established, the infant should be maintained in or transferred to an environment in which close monitoring and anticipatory care can be provided. Glucose Hypoglycaemia was associated with adverse neurological outcome in a neonatal animal model of asphyxia and resuscitation.287 Newborn animals that were hypoglycaemic at the time of an anoxic or hypoxic-ischemic insult had larger areas of cerebral infarction and/or decreased survival compared to controls.288,289 One clinical study demonstrated an association between hypoglycaemia and poor neurological outcome following perinatal asphyxia.290 In adults, children and extremely low-birth-weight infants receiving intensive care, hyperglycaemia has been associated with a worse outcome.288–292 However, in paediatric patients, hyperglycaemia after hypoxia-ischaemia does not appear to be harmful,293 which confirms data from animal studies294 some of which suggest it may be protective.295 However, the range of blood glucose concentration that is associated with the least brain injury following asphyxia and resuscitation cannot be defined based on available evidence. Infants who require significant resuscitation should be monitored and treated to maintain glucose in the normal range. Induced hypothermia Newly born infants born at term or near-term with evolving moderate to severe hypoxic - ischemic encephalopathy should, where possible, be offered therapeutic hypothermia.296–301 Whole body cooling and selective head cooling are both appropriate strategies. Cooling should be initiated and conducted under clearly defined protocols with treatment in neonatal intensive care facilities and with the capabilities for multidisciplinary care. Treatment should be consistent with the protocols used in the randomized clinical trials (i.e. commence within 6 h of birth, continue for 72 h of birth and re-warm over at least 4 h). Animal data would strongly suggest that the effectiveness of cooling is related to early intervention. There is no evidence in human newborns that cooling is effective if started more than 6 h after birth. Commencing cooling treatment >6 h after birth is at the discretion of the treating team and should only be on an individualised basis. Carefully monitor for known adverse effects of cooling such as thrombocytopenia and hypotension. All treated infants should be followed longitudinally. Prognostic tools The Apgar score was proposed as a “simple, common, clear classification or grading of newborn infants” to be used “as a basis for discussion and comparison of the results of obstetric practices, types of maternal pain relief and the effects of resuscitation” (our emphasis).106 Although widely used in clinical practice, for research purposes and as a prognostic tool,302 its applicability has been questioned due to large inter- and intra-observer variations. These are partly explained by a lack of agreement on how to score infants receiving medical interventions or being born preterm. Therefore a development of the score was recommended as follows: all parameters are scored according to the conditions regardless of the interventions needed to achieve the condition and considering whether being appropriate for gestational age. In addition, the interventions needed to achieve the condition have to be scored as well. This Combined-Apgar has been shown to predict outcome in preterm and term infants better than the conventional score.303,304 Briefing/debriefing Prior to resuscitation it is important to discuss the responsibilities of each member of the team. After the management in the delivery room a team debrief of the event using positive and constructive critique techniques should be conducted and personal bereavement counselling offered to those with a particular need. Studies of the effect of briefings or debriefings following resuscitation have generally shown improved subsequent performance.305–310 However, many of these have been following simulation training. A method that seems to further improve the management in the delivery room is videotaping and subsequent analysis of the videos.311 A structured analysis of perinatal management with feedback has been shown to improve outcomes, reducing the incidence of intraventricular haemorrhage in preterm infants.312 Regardless of the outcome, witnessing the resuscitation of their baby may be distressing for parents. Every opportunity should be taken to prepare parents for the possibility of a resuscitative effort when it is anticipated and to keep them informed as much as possible during and certainly after the resuscitation. Whenever possible, information should be given by a senior clinician. Early contact between parents and their baby is important. Conflicts of interest Jonathan Wyllie No conflict of interest reported Berndt Urlesberger No conflict of interest reported Charles Christoph Roehr Educational grant Fischer&Paykel and Medical advisor STEPHAN company Daniele Trevisanuto No conflict of interest reported Jos Bruinenberg No conflict of interest reported Mario Rüdiger Speakers honorarium Chiesi, Lyomark and Research grant SLE device Acknowledgements The Writing Group acknowledges the significant contributions to this chapter by the late Sam Richmond. References 1. Wyllie J, Perlman JM, Kattwinkel J, et al. Part 7: Neonatal resuscitation: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Resuscitation 2015;95:e171–203. 2. Perlman JM, Wyllie J, Kattwinkel J, et al. Part 7: Neonatal resuscitation: 2015 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Circulation. In press. 3. Richmond S, Wyllie J. European resuscitation council guidelines for resuscitation 2010 section 7. Resuscitation of babies at birth. Resuscitation 2010;81:1389–99. 4. Wyllie J, Perlman JM, Kattwinkel J, et al. Part 11: Neonatal resuscitation: 2010 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Resuscitation 2010;81:Se260–87 [Suppl 1]. 5. Ersdal HL, Mduma E, Svensen E, Perlman JM. Early initiation of basic resuscitation interventions including face mask ventilation may reduce birth asphyxia related mortality in low-income countries: a prospective descriptive observational study. Resuscitation 2012;83:869–73. 6. Perlman JM, Risser R. Cardiopulmonary resuscitation in the delivery room: associated clinical events. Arch Pediatr Adolesc Med 1995;149:20–5. J. Wyllie et al. / Resuscitation 95 (2015) 249–263 259 7. Barber CA, Wyckoff MH. Use and efficacy of endotracheal versus intravenous epinephrine during neonatal cardiopulmonary resuscitation in the delivery room. Pediatrics 2006;118:1028–34. 8. Palme-Kilander C. Methods of resuscitation in low-Apgar-score newborn infants—a national survey. Acta Paediatr 1992;81:739–44. 9. Aziz K, Chadwick M, Baker M, Andrews W. Ante- and intra-partum factors that predict increased need for neonatal resuscitation. Resuscitation 2008;79:444–52. 10. Yee W, Amin H, Wood S. Elective cesarean delivery, neonatal intensive care unit admission, and neonatal respiratory distress. Obstet Gynecol 2008;111:823–8. 11. Chiosi C. Genetic drift. Hospital deliveries. Am J Med Genet A 2013; 161A:2122–3. 12. Ertugrul S, Gun I, Mungen E, Muhcu M, Kilic S, Atay V. Evaluation of neonatal outcomes in elective repeat cesarean delivery at term according to weeks of gestation. J Obstet Gynaecol Res 2013;39:105–12. 13. Berthelot-Ricou A, Lacroze V, Courbiere B, Guidicelli B, Gamerre M, Simeoni U. Respiratory distress syndrome after elective caesarean section in near term infants: a 5-year cohort study. J Matern Fetal Neonatal Med 2013;26:176–82. 14. Gordon A, McKechnie EJ, Jeffery H. Pediatric presence at cesarean section: justified or not? Am J Obstet Gynecol 2005;193:599–605. 15. Atherton N, Parsons SJ, Mansfield P. Attendance of paediatricians at elective caesarean sections performed under regional anaesthesia: is it warranted? J Paediatr Child Health 2006;42:332–6. 16. Annibale DJ, Hulsey TC, Wagner CL, Southgate WM. Comparative neonatal morbidity of abdominal and vaginal deliveries after uncomplicated pregnancies. Arch Pediatr Adolesc Med 1995;149:862–7. 17. Parsons SJ, Sonneveld S, Nolan T. Is a paediatrician needed at all caesarean sections? J Paediatr Child Health 1998;34:241–4. 18. Peltonen T. Placental transfusion—advantage an disadvantage. Eur J Pediatr 1981;137:141–6. 19. Brady JP, James LS. Heart rate changes in the fetus and newborn infant during labor, delivery, and the immediate neonatal period. Am J Obstet Gynecol 1962;84:1–12. 20. Polglase GR, Dawson JA, Kluckow M, et al. Ventilation onset prior to umbilical cord clamping (physiological-based cord clamping) improves systemic and cerebral oxygenation in preterm lambs. PloS One 2015;10:e0117504. 21. Strauss RG, Mock DM, Johnson KJ, et al. A randomized clinical trial comparing immediate versus delayed clamping of the umbilical cord in preterm infants: short-term clinical and laboratory endpoints. Transfusion 2008;48:658–65. 22. Rabe H, Reynolds G, Diaz-Rossello J. A systematic review and meta-analysis of a brief delay in clamping the umbilical cord of preterm infants. Neonatology 2008;93:138–44. 23. Ghavam S, Batra D, Mercer J, et al. Effects of placental transfusion in extremely low birthweight infants: meta-analysis of long- and short-term outcomes. Transfusion 2014;54:1192–8. 24. Mercer JS, Vohr BR, McGrath MM, Padbury JF, Wallach M, Oh W. Delayed cord clamping in very preterm infants reduces the incidence of intraventricular hemorrhage and late-onset sepsis: a randomized, controlled trial. Pediatrics 2006;117:1235–42. 25. Kugelman A, Borenstein-Levin L, Riskin A, et al. Immediate versus delayed umbilical cord clamping in premature neonates born <35 weeks: a prospective, randomized, controlled study. Am J Perinatol 2007;24:307–15. 26. Katheria AC, Truong G, Cousins L, Oshiro B, Finer NN. Umbilical cord milking versus delayed cord clamping in preterm infants. Pediatrics 2015;136:61–9. 27. Dahm LS, James LS. Newborn temperature and calculated heat loss in the delivery room. Pediatrics 1972;49:504–13. 28. Stephenson J, Du JTKO. The effect if cooling on blood gas tensions in newborn infants. J Pediatr 1970;76:848–52. 29. Gandy GM, Adamsons Jr K, Cunningham N, Silverman WA, James LS. Thermal environment and acid-base homeostasis in human infants during the first few hours of life. J Clin Invest 1964;43:751–8. 30. Budin P [Translation by WJ Maloney] The nursling. The feeding and hygiene of premature and full-term infants. London: The Caxton Publishing Company; 1907. 31. Abd-El Hamid S, Badr-El Din MM, Dabous NI, Saad KM. Effect of the use of a polyethylene wrap on the morbidity and mortality of very low birth weight infants in Alexandria University Children’s Hospital. J Egypt Public Health Assoc 2012;87:104–8. 32. Acolet D, Elbourne D, McIntosh N, et al. Project 27/28: inquiry into quality of neonatal care and its effect on the survival of infants who were born at 27 and 28 weeks in England, Wales, and Northern Ireland. Pediatrics 2005;116:1457–65. 33. Bateman DA, O’Bryan L, Nicholas SW, Heagarty MC. Outcome of unattended out-of-hospital births in Harlem. Arch Pediatr Adolesc Med 1994;148:147–52. 34. Bhoopalam PS, Watkinson M. Babies born before arrival at hospital. Br J Obstet Gynaecol 1991;98:57–64. 35. Boo NY, Guat-Sim Cheah I, Malaysian National Neonatal Registry. Admission hypothermia among VLBW infants in Malaysian NICUs. J Trop Pediatr 2013;59:447–52. 36. Buetow KC, Kelein SW. Effects of maintenenance of “normal” skin temperature on survival of infants of low birth weight. Pediatrics 1964;33:163–9. 37. Costeloe K, Hennessy E, Gibson AT, Marlow N, Wilkinson AR. The EPICure study: outcomes to discharge from hospital for infants born at the threshold of viability. Pediatrics 2000;106:659–71. 38. Costeloe KL, Hennessy EM, Haider S, Stacey F, Marlow N, Draper ES. Short term outcomes after extreme preterm birth in England: comparison of two birth cohorts in 1995 and 2006 (the EPICure studies). BMJ 2012;345:e7976. 39. da Mota Silveira SM, Goncalves de Mello MJ, de Arruda Vidal S, de Frias PG, Cattaneo A. Hypothermia on admission: a risk factor for death in newborns referred to the Pernambuco Institute of Mother And Child Health. J Trop Pediatr 2003;49:115–20. 40. Daga AS, Daga SR, Patole SK. Determinants of death among admissions to intensive care unit for newborns. J Trop Pediatr 1991;37:53–6. 41. de Almeida MF, Guinsburg R, Sancho GA, et al. Hypothermia and early neonatal mortality in preterm infants. J Pediatr 2014;164:e1271–5. 42. Garcia-Munoz Rodrigo F, Rivero Rodriguez S, Siles Quesada C. Hypothermia risk factors in the very low weight newborn and associated morbidity and mortality in a neonatal care unit. An Pediatr (Barc) 2014;80:144–50. 43. Harms K, Osmers R, Kron M, et al. Mortality of premature infants 1980–1990: analysis of data from the Gottingen perinatal center. Z Geburtshilfe Perinatol 1994;198:126–33. 44. Hazan J, Maag U, Chessex P. Association between hypothermia and mortality rate of premature infants—revisited. Am J Obstet Gynecol 1991;164:111–2. 45. Jones P, Alberti C, Jule L, et al. Mortality in out-of-hospital premature births. Acta Paediatr 2011;100:181–7. 46. Kalimba E, Ballot D. Survival of extremely low-birth-weight infants. S Afr J Child Health 2013;7:13–6. 47. Kambarami R, Chidede O. Neonatal hypothermia levels and risk factors for mortality in a tropical country. Cent Afr J Med 2003;49:103–6. 48. Kent AL, Williams J. Increasing ambient operating theatre temperature and wrapping in polyethylene improves admission temperature in premature infants. J Paediatr Child Health 2008;44:325–31. 49. Laptook AR, Salhab W, Bhaskar B, Neonatal Research Network. Admission temperature of low birth weight infants: predictors and associated morbidities. Pediatrics 2007;119:e643–9. 50. Lee HC, Ho QT, Rhine WD. A quality improvement project to improve admission temperatures in very low birth weight infants. J Perinatol: Off J California Perinat Assoc 2008;28:754–8. 51. Levi S, Taylor W, Robinson LE, Levy LI. Analysis of morbidity and outcome of infants weighing less than 800 grams at birth. S Med J 1984;77:975–8. 52. Manani M, Jegatheesan P, DeSandre G, Song D, Showalter L, Govindaswami B. Elimination of admission hypothermia in preterm very low-birth-weight infants by standardization of delivery room management. Permanente J 2013;17:8–13. 53. Manji KP, Kisenge R. Neonatal hypothermia on admission to a special care unit in Dar-es-Salaam, Tanzania: a cause for concern. Cent Afr J Med 2003;49:23–7. 54. Mathur NB, Krishnamurthy S, Mishra TK. Evaluation of WHO classification of hypothermia in sick extramural neonates as predictor of fatality. J Trop Pediatr 2005;51:341–5. 55. Miller SS, Lee HC, Gould JB. Hypothermia in very low birth weight infants: distribution, risk factors and outcomes. J Perinatol: Off J California Perinat Assoc 2011;31:S49–56 [Suppl 1]. 56. Mullany LC, Katz J, Khatry SK, LeClerq SC, Darmstadt GL, Tielsch JM. Risk of mortality associated with neonatal hypothermia in southern Nepal. Arch Pediatr Adolesc Med 2010;164:650–6. 57. Nayeri F, Nili F. Hypothermia at birth and its associated complications in newborn infants: a follow up study. Iranian J Public Health 2006;35:48–52. 58. Obladen M, Heemann U, Hennecke KH, Hanssler L. Causes of neonatal mortality 1981–1983: a regional analysis. Z Geburtshilfe Perinatol 1985;189:181–7. 59. Ogunlesi TA, Ogunfowora OB, Adekanmbi FA, Fetuga BM, Olanrewaju DM. Point-of-admission hypothermia among high-risk Nigerian newborns. BMC Pediatr 2008;8:40. 60. Pal DK, Manandhar DS, Rajbhandari S, Land JM, Patel N, de LCAM. Neonatal hypoglycaemia in Nepal 1. Prevalence and risk factors. Arch Dis Child Fetal Neonatal Ed 2000;82. F46-F51. 61. Shah S, Zemichael O, Meng HD. Factors associated with mortality and length of stay in hospitalised neonates in Eritrea, Africa: a cross-sectional study. BMJ Open 2012;2:2, pii: e000792. 62. Singh A, Yadav A, Singh A. Utilization of postnatal care for newborns and its association with neonatal mortality in India: an analytical appraisal. BMC Pregnancy Childbirth 2012;12:33. 63. Sodemann M, Nielsen J, Veirum J, Jakobsen MS, Biai S, Aaby P. Hypothermia of newborns is associated with excess mortality in the first 2 months of life in Guinea-Bissau, West Africa. Trop Med Int Health 2008;13:980–6. 64. Stanley FJ, Alberman EV. Infants of very low birthweight, I: perinatal factors affecting survival. Dev Med Child Neurol 1978;20:300–12. 65. Wyckoff MH, Perlman JM. Effective ventilation and temperature control are vital to outborn resuscitation. Prehosp Emerg Care: Off J Natl Assoc EMS Phys Natl Assoc State EMS Dir 2004;8:191–5. 66. Bartels DB, Kreienbrock L, Dammann O, Wenzlaff P, Poets CF. Population based study on the outcome of small for gestational age newborns. Arch Dis Child Fetal Neonatal Ed 2005;90:F53–9. 67. Carroll PD, Nankervis CA, Giannone PJ, Cordero L. Use of polyethylene bags in extremely low birth weight infant resuscitation for the prevention of hypothermia. J Reprod Med 2010;55:9–13. 68. Gleissner M, Jorch G, Avenarius S. Risk factors for intraventricular hemorrhage in a birth cohort of 3721 premature infants. J Perinat Med 2000;28:104–10. 69. Herting E, Speer CP, Harms K, et al. Factors influencing morbidity and mortality in infants with severe respiratory distress syndrome treated with single or multiple doses of a natural porcine surfactant. Biol Neonate 1992;61:S26–30 [Suppl 1]. 70. DeMauro SB, Douglas E, Karp K, et al. Improving delivery room management for very preterm infants. Pediatrics 2013;132:e1018–25. 260 J. Wyllie et al. / Resuscitation 95 (2015) 249–263 71. Harms K, Herting E, Kron M, Schill M, Schiffmann H. Importance of preand perinatal risk factors in respiratory distress syndrome of premature infants. A logical regression analysis of 1100 cases. Z Geburtshilfe Neonatol 1997;201:258–62. 72. Lee HC, Powers RJ, Bennett MV, et al. Implementation methods for delivery room management: a quality improvement comparison study. Pediatrics 2014;134:e1378–86. 73. Reilly MC, Vohra S, Rac VE, et al. Randomized trial of occlusive wrap for heat loss prevention in preterm infants. J Pediatr 2015;166:e2262–8. 74. Zayeri F, Kazemnejad A, Ganjali M, Babaei G, Khanafshar N, Nayeri F. Hypothermia in Iranian newborns, Incidence, risk factors and related complications. Saudi Med J 2005;26:1367–71. 75. Anderson S, Shakya KN, Shrestha LN, Costello AM. Hypoglycaemia: a common problem among uncomplicated newborn infants in Nepal. J Trop Pediatr 1993;39:273–7. 76. Lazic-Mitrovic T, Djukic M, Cutura N, et al. Transitory hypothermia as early prognostic factor in term newborns with intrauterine growth retardation. Srp Arh Celok Lek 2010;138:604–8. 77. Lenclen R, Mazraani M, Jugie M, et al. Use of a polyethylene bag: a way to improve the thermal environment of the premature newborn at the delivery room. Arch Pediatr 2002;9:238–44. 78. Sasidharan CK, Gokul E, Sabitha S. Incidence and risk factors for neonatal hypoglycaemia in Kerala, India. Ceylon Med J 2004;49:110–3. 79. Mullany LC. Neonatal hypothermia in low-resource settings. Semin Perinatol 2010;34:426–33. 80. World Health Organization: Department of Reproductive Health and Research (RHR). Thermal protection of the newborn: a practical guide (WHO/RHT/MSM/97.2). Geneva; 1997. 81. See ref. 27. 82. Vohra S, Frent G, Campbell V, Abbott M, Whyte R. Effect of polyethylene occlusive skin wrapping on heat loss in very low birth weight infants at delivery: a randomized trial. J Pediatr 1999;134:547–51. 83. Bjorklund LJ, Hellstrom-Westas L. Reducing heat loss at birth in very preterm infants. J Pediatr 2000;137:739–40. 84. Meyer MP, Payton MJ, Salmon A, Hutchinson C, de Klerk A. A clinical comparison of radiant warmer and incubator care for preterm infants from birth to 1800 grams. Pediatrics 2001;108:395–401. 85. te Pas AB, Lopriore E, Dito I, Morley CJ, Walther FJ. Humidified and heated air during stabilization at birth improves temperature in preterm infants. Pediatrics 2010;125:e1427–32. 86. Russo A, McCready M, Torres L, et al. Reducing hypothermia in preterm infants following delivery. Pediatrics 2014;133:e1055–62. 87. Pinheiro JM, Furdon SA, Boynton S, Dugan R, Reu-Donlon C, Jensen S. Decreasing hypothermia during delivery room stabilization of preterm neonates. Pediatrics 2014;133:e218–26. 88. McCarthy LK, Molloy EJ, Twomey AR, Murphy JF, O’Donnell CP. A randomized trial of exothermic mattresses for preterm newborns in polyethylene bags. Pediatrics 2013;132:e135–41. 89. Billimoria Z, Chawla S, Bajaj M, Natarajan G. Improving admission temperature in extremely low birth weight infants: a hospital-based multi-intervention quality improvement project. J Perinat Med 2013;41:455–60. 90. Chawla S, Amaram A, Gopal SP, Natarajan G. Safety and efficacy of transwarmer mattress for preterm neonates: results of a randomized controlled trial. J Perinatol: Off J California Perinat Assoc 2011;31:780–4. 91. Ibrahim CP, Yoxall CW. Use of self-heating gel mattresses eliminates admission hypothermia in infants born below 28 weeks gestation. Eur J Pediatr 2010;169:795–9. 92. Singh A, Duckett J, Newton T, Watkinson M. Improving neonatal unit admission temperatures in preterm babies: exothermic mattresses, polythene bags or a traditional approach? J Perinatol: Off J California Perinat Assoc 2010;30:45–9. 93. Belsches TC, Tilly AE, Miller TR, et al. Randomized trial of plastic bags to prevent term neonatal hypothermia in a resource-poor setting. Pediatrics 2013;132:e656–61. 94. Leadford AE, Warren JB, Manasyan A, et al. Plastic bags for prevention of hypothermia in preterm and low birth weight infants. Pediatrics 2013;132:e128–34. 95. Bergman NJ, Linley LL, Fawcus SR. Randomized controlled trial of skin-to-skin contact from birth versus conventional incubator for physiological stabilization in 1200- to 2199-gram newborns. Acta Paediatr 2004;93:779–85. 96. Fardig JA. A comparison of skin-to-skin contact and radiant heaters in promoting neonatal thermoregulation. J Nurse-Midwifery 1980;25:19–28. 97. Christensson K, Siles C, Moreno L, et al. Temperature, metabolic adaptation and crying in healthy full-term newborns cared for skin-to-skin or in a cot. Acta Paediatr 1992;81:488–93. 98. Christensson K. Fathers can effectively achieve heat conservation in healthy newborn infants. Acta Paediatr 1996;85:1354–60. 99. Bystrova K, Widstrom AM, Matthiesen AS, et al. Skin-to-skin contact may reduce negative consequences of “the stress of being born”: a study on temperature in newborn infants, subjected to different ward routines in St. Petersburg. Acta Paediatr 2003;92:320–6. 100. Nimbalkar SM, Patel VK, Patel DV, Nimbalkar AS, Sethi A, Phatak A. Effect of early skin-to-skin contact following normal delivery on incidence of hypothermia in neonates more than 1800 g: randomized control trial. J Perinatol: Off J California Perinat Assoc 2014;34:364–8. 101. Marin Gabriel MA, Llana Martin I, Lopez Escobar A, Fernandez Villalba E, Romero Blanco I, Touza Pol P. Randomized controlled trial of early skin-to-skin contact: effects on the mother and the newborn. Acta Paediatr 2010;99:1630–4. 102. Lieberman E, Eichenwald E, Mathur G, Richardson D, Heffner L, Cohen A. Intrapartum fever and unexplained seizures in term infants. Pediatrics 2000;106:983–8. 103. Grether JK, Nelson KB. Maternal infection and cerebral palsy in infants of normal birth weight. JAMA 1997;278:207–11. 104. Coimbra C, Boris-Moller F, Drake M, Wieloch T. Diminished neuronal damage in the rat brain by late treatment with the antipyretic drug dipyrone or cooling following cerebral ischemia. Acta Neuropathol 1996;92:447–53. 105. Dietrich WD, Alonso O, Halley M, Busto R. Delayed posttraumatic brain hyperthermia worsens outcome after fluid percussion brain injury: a light and electron microscopic study in rats. Neurosurgery 1996;38:533–41 [discussion 41]. 106. Apgar V. A proposal for a new method of evaluation of the newborn infant. Curr Res Anesth Analg 1953;32:260–7. 107. Chamberlain G, Banks J. Assessment of the Apgar score. Lancet 1974;2:1225–8. 108. Owen CJ, Wyllie JP. Determination of heart rate in the baby at birth. Resuscitation 2004;60:213–7. 109. Kamlin CO, O’Donnell CP, Everest NJ, Davis PG, Morley CJ. Accuracy of clinical assessment of infant heart rate in the delivery room. Resuscitation 2006;71:319–21. 110. Dawson JA, Saraswat A, Simionato L, et al. Comparison of heart rate and oxygen saturation measurements from Masimo and Nellcor pulse oximeters in newly born term infants. Acta Paediatr 2013;102:955–60. 111. Kamlin CO, Dawson JA, O’Donnell CP, et al. Accuracy of pulse oximetry measurement of heart rate of newborn infants in the delivery room. J Pediatr 2008;152:756–60. 112. Katheria A, Rich W, Finer N. Electrocardiogram provides a continuous heart rate faster than oximetry during neonatal resuscitation. Pediatrics 2012;130:e1177–81. 113. Voogdt KG, Morrison AC, Wood FE, van Elburg RM, Wyllie JP. A randomised, simulated study assessing auscultation of heart rate at birth. Resuscitation 2010;81:1000–3. 114. Mizumoto H, Tomotaki S, Shibata H, et al. Electrocardiogram shows reliable heart rates much earlier than pulse oximetry during neonatal resuscitation. Pediatr Int 2012;54:205–7. 115. van Vonderen JJ, Hooper SB, Kroese JK, et al. Pulse oximetry measures a lower heart rate at birth compared with electrocardiography. J Pediatr 2015;166:49–53. 116. O’Donnell CP, Kamlin CO, Davis PG, Carlin JB, Morley CJ. Clinical assessment of infant colour at delivery. Arch Dis Child Fetal Neonatal Ed 2007;92:F465–7. 117. Konstantelos D, Gurth H, Bergert R, Ifflaender S, Rudiger M. Positioning of term infants during delivery room routine handling—analysis of videos. BMC Pediatr 2014;14:33. 118. Kelleher J, Bhat R, Salas AA, et al. Oronasopharyngeal suction versus wiping of the mouth and nose at birth: a randomised equivalency trial. Lancet 2013;382:326–30. 119. Cordero Jr L, Hon EH. Neonatal bradycardia following nasopharyngeal stimulation. J Pediatr 1971;78:441–7. 120. Gungor S, Kurt E, Teksoz E, Goktolga U, Ceyhan T, Baser I. Oronasopharyngeal suction versus no suction in normal and term infants delivered by elective cesarean section: a prospective randomized controlled trial. Gynecol Obstet Invest 2006;61:9–14. 121. Waltman PA, Brewer JM, Rogers BP, May WL. Building evidence for practice: a pilot study of newborn bulb suctioning at birth. J Midwifery Womens Health 2004;49:32–8. 122. Carson BS, Losey RW, Bowes Jr WA, Simmons MA. Combined obstetric and pediatric approach to prevent meconium aspiration syndrome. Am J Obstet Gynecol 1976;126:712–5. 123. Ting P, Brady JP. Tracheal suction in meconium aspiration. Am J Obstet Gynecol 1975;122:767–71. 124. Falciglia HS, Henderschott C, Potter P, Helmchen R. Does DeLee suction at the perineum prevent meconium aspiration syndrome? Am J Obstet Gynecol 1992;167:1243–9. 125. Wiswell TE, Tuggle JM, Turner BS. Meconium aspiration syndrome: have we made a difference? Pediatrics 1990;85:715–21. 126. Wiswell TE, Gannon CM, Jacob J, et al. Delivery room management of the apparently vigorous meconium-stained neonate: results of the multicenter, international collaborative trial. Pediatrics 2000;105:1–7. 127. Vain NE, Szyld EG, Prudent LM, Wiswell TE, Aguilar AM, Vivas NI. Oropharyngeal and nasopharyngeal suctioning of meconium-stained neonates before delivery of their shoulders: multicentre, randomised controlled trial. Lancet 2004;364:597–602. 128. Chettri S, Adhisivam B, Bhat BV. Endotracheal suction for nonvigorous neonates born through meconium stained amniotic fluid: a randomized controlled trial. J Pediatr 2015;166:1208–13. 129. Al Takroni AM, Parvathi CK, Mendis KB, Hassan S, Reddy I, Kudair HA. Selective tracheal suctioning to prevent meconium aspiration syndrome. Int J Gynaecol Obstet 1998;63:259–63. 130. Davis RO, Philips 3rd JB, Harris Jr BA, Wilson ER, Huddleston JF. Fatal meconium aspiration syndrome occurring despite airway management considered appropriate. Am J Obstet Gynecol 1985;151:731–6. 131. Manganaro R, Mami C, Palmara A, Paolata A, Gemelli M. Incidence of meconium aspiration syndrome in term meconium-stained babies managed at birth with selective tracheal intubation. J Perinat Med 2001;29:465–8. J. Wyllie et al. / Resuscitation 95 (2015) 249–263 261 132. Yoder BA. Meconium-stained amniotic fluid and respiratory complications: impact of selective tracheal suction. Obstet Gynecol 1994;83:77–84. 133. Bent RC, Wiswell TE, Chang A. Removing meconium from infant tracheae. What works best? Am J Dis Child 1992;146:1085–9. 134. Dargaville PA, Copnell B, Mills JF, et al. Randomized controlled trial of lung lavage with dilute surfactant for meconium aspiration syndrome. J Pediatr 2011;158:e2383–9. 135. Dargaville PA, Copnell B, Mills JF, et al. Fluid recovery during lung lavage in meconium aspiration syndrome. Acta Paediatr 2013;102:e90–3. 136. Wyllie J, Perlman JM, Kattwinkel J, et al. Part 11: neonatal resuscitation: 2010 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations. Resuscitation 2010;81:Se260–87 [Suppl 1]. 137. Vyas H, Milner AD, Hopkin IE, Boon AW. Physiologic responses to prolonged and slow-rise inflation in the resuscitation of the asphyxiated newborn infant. J Pediatr 1981;99:635–9. 138. Mortola JP, Fisher JT, Smith JB, Fox GS, Weeks S, Willis D. Onset of respiration in infants delivered by cesarean section. J Appl Physiol 1982;52:716–24. 139. Hull D. Lung expansion and ventilation during resuscitation of asphyxiated newborn infants. J Pediatr 1969;75:47–58. 140. Vyas H, Milner AD, Hopkins IE. Intrathoracic pressure and volume changes during the spontaneous onset of respiration in babies born by cesarean section and by vaginal delivery. J Pediatr 1981;99:787–91. 141. Vyas H, Field D, Milner AD, Hopkin IE. Determinants of the first inspiratory volume and functional residual capacity at birth. Pediatr Pulmonol 1986;2:189–93. 142. Boon AW, Milner AD, Hopkin IE. Lung expansion, tidal exchange, and formation of the functional residual capacity during resuscitation of asphyxiated neonates. J Pediatr 1979;95:1031–6. 143. Hird MF, Greenough A, Gamsu HR. Inflating pressures for effective resuscitation of preterm infants. Early Hum Dev 1991;26:69–72. 144. Lindner W, Vossbeck S, Hummler H, Pohlandt F. Delivery room management of extremely low birth weight infants: spontaneous breathing or intubation? Pediatrics 1999;103:961–7. 145. Wood FE, Morley CJ, Dawson JA, et al. Assessing the effectiveness of two round neonatal resuscitation masks: study 1. Arch Dis Child Fetal Neonatal Ed 2008;93:F235–7. 146. Wood FE, Morley CJ, Dawson JA, et al. Improved techniques reduce face mask leak during simulated neonatal resuscitation: study 2. Arch Dis Child Fetal Neonatal Ed 2008;93:F230–4. 147. Tracy MB, Klimek J, Coughtrey H, et al. Mask leak in one-person mask ventilation compared to two-person in newborn infant manikin study. Arch Dis Child Fetal Neonatal Ed 2011;96:F195–200. 148. Schmolzer GM, Dawson JA, Kamlin CO, O’Donnell CP, Morley CJ, Davis PG. Airway obstruction and gas leak during mask ventilation of preterm infants in the delivery room. Arch Dis Child Fetal Neonatal Ed 2011;96:F254–7. 149. Schmolzer GM, Kamlin OC, O’Donnell CP, Dawson JA, Morley CJ, Davis PG. Assessment of tidal volume and gas leak during mask ventilation of preterm infants in the delivery room. Arch Dis Child Fetal Neonatal Ed 2010;95: F393–7. 150. Klingenberg C, Sobotka KS, Ong T, et al. Effect of sustained inflation duration; resuscitation of near-term asphyxiated lambs. Arch Dis Child Fetal Neonatal Ed 2013;98:F222–7. 151. te Pas AB, Siew M, Wallace MJ, et al. Effect of sustained inflation length on establishing functional residual capacity at birth in ventilated premature rabbits. Pediatr Res 2009;66:295–300. 152. Harling AE, Beresford MW, Vince GS, Bates M, Yoxall CW. Does sustained lung inflation at resuscitation reduce lung injury in the preterm infant? Arch Dis Child Fetal Neonatal Ed 2005;90:F406–10. 153. Lindner W, Hogel J, Pohlandt F. Sustained pressure-controlled inflation or intermittent mandatory ventilation in preterm infants in the delivery room? A randomized, controlled trial on initial respiratory support via nasopharyngeal tube. Acta Paediatr 2005;94:303–9. 154. Lista G, Boni L, Scopesi F, et al. Sustained lung inflation at birth for preterm infants: a randomized clinical trial. Pediatrics 2015;135:e457–64. 155. Lista G, Fontana P, Castoldi F, Cavigioli F, Dani C. Does sustained lung inflation at birth improve outcome of preterm infants at risk for respiratory distress syndrome? Neonatology 2011;99:45–50. 156. Mariani G, Dik PB, Ezquer A, et al. Pre-ductal and post-ductal O2 saturation in healthy term neonates after birth. J Pediatr 2007;150:418–21. 157. Dawson JA, Kamlin CO, Vento M, et al. Defining the reference range for oxygen saturation for infants after birth. Pediatrics 2010;125:e1340–7. 158. Davis PG, Tan A, O’Donnell CP, Schulze A. Resuscitation of newborn infants with 100% oxygen or air: a systematic review and meta-analysis. Lancet 2004;364:1329–33. 159. Vento M, Moro M, Escrig R, et al. Preterm resuscitation with low oxygen causes less oxidative stress, inflammation, and chronic lung disease. Pediatrics 2009;4. 160. Saugstad OD, Aune D, Aguar M, Kapadia V, Finer N, Vento M. Systematic review and meta-analysis of optimal initial fraction of oxygen levels in the delivery room at <=32 weeks. Acta Paediatr 2014;103:744–51. 161. Armanian AM, Badiee Z. Resuscitation of preterm newborns with low concentration oxygen versus high concentration oxygen. J Res Pharm Pract 2012;1:25–9. 162. Kapadia VS, Chalak LF, Sparks JE, Allen JR, Savani RC, Wyckoff MH. Resuscitation of preterm neonates with limited versus high oxygen strategy. Pediatrics 2013;132:e1488–96. 163. Lundstrom KE, Pryds O, Greisen G. Oxygen at birth and prolonged cerebral vasoconstriction in preterm infants. Arch Dis Child Fetal Neonatal Ed 1995;73. F81-F6. 164. Rabi Y, Singhal N, Nettel-Aguirre A. Room-air versus oxygen administration for resuscitation of preterm infants: the ROAR study. Pediatrics 2011;128:e374–81. 165. Rook D, Schierbeek H, Vento M, et al. Resuscitation of preterm infants with different inspired oxygen fractions. J Pediatr 2014;164:e31322–6. 166. Wang CL, Anderson C, Leone TA, Rich W, Govindaswami B, Finer NN. Resuscitation of preterm neonates by using room air or 100% oxygen. Pediatrics 2008;121:1083–9. 167. O’Donnell CP, Kamlin CO, Davis PG, Morley CJ. Feasibility of and delay in obtaining pulse oximetry during neonatal resuscitation. J Pediatr 2005;147: 698–9. 168. Dawson JA, Kamlin CO, Wong C, et al. Oxygen saturation and heart rate during delivery room resuscitation of infants <30 weeks’ gestation with air or 100% oxygen. Arch Dis Child Fetal Neonatal Ed 2009;94:F87–91. 169. Dildy GA, van den Berg PP, Katz M, et al. Intrapartum fetal pulse oximetry: fetal oxygen saturation trends during labor and relation to delivery outcome. Am J Obstet Gynecol 1994;171:679–84. 170. Rabi Y, Yee W, Chen SY, Singhal N. Oxygen saturation trends immediately after birth. J Pediatr 2006;148:590–4. 171. Gonzales GF, Salirrosas A. Arterial oxygen saturation in healthy newborns delivered at term in Cerro de Pasco (4340 m) and Lima (150 m). Reprod Biol Endocrinol 2005;3:46. 172. Smit M, Dawson JA, Ganzeboom A, Hooper SB, van Roosmalen J, te Pas AB. Pulse oximetry in newborns with delayed cord clamping and immediate skin-to-skin contact. Arch Dis Child Fetal Neonatal Ed 2014;99:F309–14. 173. Deleted in proof. 174. Ingimarsson J, Bjorklund LJ, Curstedt T, et al. Incomplete protection by prophylactic surfactant against the adverse effects of large lung inflations at birth in immature lambs. Intensive Care Med 2004;30:1446–53. 175. Muscedere JG, Mullen JB, Gan K, Slutsky AS. Tidal ventilation at low airway pressures can augment lung injury. Am J Respir Crit Care Med 1994;149: 1327–34. 176. Naik AS, Kallapur SG, Bachurski CJ, et al. Effects of ventilation with different positive end-expiratory pressures on cytokine expression in the preterm lamb lung. Am J Respir Crit Care Med 2001;164:494–8. 177. Polglase GR, Hillman NH, Pillow JJ, et al. Positive end-expiratory pressure and tidal volume during initial ventilation of preterm lambs. Pediatr Res 2008;64:517–22. 178. Nilsson R, Grossmann G, Robertson B. Bronchiolar epithelial lesions induced in the premature rabbit neonate by short periods of artificial ventilation. Acta Pathol Microbiol Scand 1980;88:359–67. 179. Probyn ME, Hooper SB, Dargaville PA, et al. Positive end expiratory pressure during resuscitation of premature lambs rapidly improves blood gases without adversely affecting arterial pressure. Pediatr Res 2004;56:198–204. 180. te Pas AB, Siew M, Wallace MJ, et al. Establishing functional residual capacity at birth: the effect of sustained inflation and positive end-expiratory pressure in a preterm rabbit model. Pediatr Res 2009;65:537–41. 181. Dawson JA, Schmolzer GM, Kamlin CO, et al. Oxygenation with T-piece versus self-inflating bag for ventilation of extremely preterm infants at birth: a randomized controlled trial. J Pediatr 2011;158:912–8 [e1–2]. 182. Szyld E, Aguilar A, Musante GA, et al. Comparison of devices for newborn ventilation in the delivery room. J Pediatr 2014;165:e3234–9. 183. Allwood AC, Madar RJ, Baumer JH, Readdy L, Wright D. Changes in resuscitation practice at birth. Arch Dis Child Fetal Neonatal Ed 2003;88:F375–9. 184. Cole AF, Rolbin SH, Hew EM, Pynn S. An improved ventilator system for delivery-room management of the newborn. Anesthesiology 1979;51:356–8. 185. Hoskyns EW, Milner AD, Hopkin IE. A simple method of face mask resuscitation at birth. Arch Dis Child 1987;62:376–8. 186. Ganga-Zandzou PS, Diependaele JF, Storme L, et al. Is Ambu ventilation of newborn infants a simple question of finger-touch? Arch Pediatr 1996;3:1270–2. 187. Oddie S, Wyllie J, Scally A. Use of self-inflating bags for neonatal resuscitation. Resuscitation 2005;67:109–12. 188. Finer NN, Rich W, Craft A, Henderson C. Comparison of methods of bag and mask ventilation for neonatal resuscitation. Resuscitation 2001;49:299–305. 189. Dawson JA, Gerber A, Kamlin CO, Davis PG, Morley CJ. Providing PEEP during neonatal resuscitation: which device is best? J Paediatr Child Health 2011;47:698–703. 190. Roehr CC, Kelm M, Fischer HS, Buhrer C, Schmalisch G, Proquitte H. Manual ventilation devices in neonatal resuscitation: tidal volume and positive pressure-provision. Resuscitation 2010;81:202–5. 191. Kanter RK. Evaluation of mask-bag ventilation in resuscitation of infants. Am J Dis Child 1987;141:761–3. 192. Morley CJ, Dawson JA, Stewart MJ, Hussain F, Davis PG. The effect of a PEEP valve on a Laerdal neonatal self-inflating resuscitation bag. J Paediatr Child Health 2010;46:51–6. 193. Bennett S, Finer NN, Rich W, Vaucher Y. A comparison of three neonatal resuscitation devices. Resuscitation 2005;67:113–8. 194. Kelm M, Proquitte H, Schmalisch G, Roehr CC. Reliability of two common PEEP-generating devices used in neonatal resuscitation. Klin Padiatr 2009;221:415–8. 195. Hartung JC, Schmolzer G, Schmalisch G, Roehr CC. Repeated thermosterilisation further affects the reliability of positive end-expiratory pressure valves. J Paediatr Child Health 2013;49:741–5. 262 J. Wyllie et al. / Resuscitation 95 (2015) 249–263 196. Schmolzer GM, Morley CJ, Wong C, et al. Respiratory function monitor guidance of mask ventilation in the delivery room: a feasibility study. J Pediatr 2012;160:e2377–81. 197. Kong JY, Rich W, Finer NN, Leone TA. Quantitative end-tidal carbon dioxide monitoring in the delivery room: a randomized controlled trial. J Pediatr 2013;163:e1104–8. 198. Leone TA, Lange A, Rich W, Finer NN. Disposable colorimetric carbon dioxide detector use as an indicator of a patent airway during noninvasive mask ventilation. Pediatrics 2006;118, e202-e204. 199. McCarthy LK, Twomey AR, Molloy EJ, Murphy JF, O’Donnell CP. A randomized trial of nasal prong or face mask for respiratory support for preterm newborns. Pediatrics 2013;132:e389–95. 200. Kamlin CO, Schilleman K, Dawson JA, et al. Mask versus nasal tube for stabilization of preterm infants at birth: a randomized controlled trial. Pediatrics 2013;132:e381–8. 201. Trevisanuto D, Cavallin F, Nguyen LN, et al. Supreme laryngeal mask airway versus face mask during neonatal resuscitation: a randomized controlled trial. J Pediatr 2015;167:286–91. 202. Esmail N, Saleh M. Laryngeal mask airway versus endotracheal intubation for Apgar score improvement in neonatal resuscitation. Egypt J Anesthesiol 2002;18:115–21. 203. Trevisanuto D, Micaglio M, Pitton M, Magarotto M, Piva D, Zanardo V. Laryngeal mask airway: is the management of neonates requiring positive pressure ventilation at birth changing? Resuscitation 2004;62:151–7. 204. Singh R. Controlled trial to evaluate the use of LMA for neonatal resuscitation. J Anaesthiol Clin Pharmacol 2005;21:303–6. 205. Zhu XY, Lin BC, Zhang QS, Ye HM, Yu RJ. A prospective evaluation of the efficacy of the laryngeal mask airway during neonatal resuscitation. Resuscitation 2011;82:1405–9. 206. Schmolzer GM, Agarwal M, Kamlin CO, Davis PG. Supraglottic airway devices during neonatal resuscitation: an historical perspective, systematic review and meta-analysis of available clinical trials. Resuscitation 2013;84:722–30. 207. Kempley ST, Moreiras JW, Petrone FL. Endotracheal tube length for neonatal intubation. Resuscitation 2008;77:369–73. 208. Gill I, O’Donnell CP. Vocal cord guides on neonatal endotracheal tubes. Arch Dis Child Fetal Neonatal Ed 2014;99:F344. 209. Palme-Kilander C, Tunell R. Pulmonary gas exchange during facemask ventilation immediately after birth. Arch Dis Child 1993;68:11–6. 210. Aziz HF, Martin JB, Moore JJ. The pediatric disposable end-tidal carbon dioxide detector role in endotracheal intubation in newborns. J Perinatol: Off J California Perinat Assoc 1999;19:110–3. 211. Bhende MS, LaCovey D. A note of caution about the continuous use of colorimetric end-tidal CO2 detectors in children. Pediatrics 1995;95:800–1. 212. Repetto JE, Donohue P-CP, Baker SF, Kelly L, Nogee LM. Use of capnography in the delivery room for assessment of endotracheal tube placement. J Perinatol: Off J California Perinat Assoc 2001;21:284–7. 213. Roberts WA, Maniscalco WM, Cohen AR, Litman RS, Chhibber A. The use of capnography for recognition of esophageal intubation in the neonatal intensive care unit. Pediatr Pulmonol 1995;19:262–8. 214. Hosono S, Inami I, Fujita H, Minato M, Takahashi S, Mugishima H. A role of end-tidal CO(2) monitoring for assessment of tracheal intubations in very low birth weight infants during neonatal resuscitation at birth. J Perinat Med 2009;37:79–84. 215. Garey DM, Ward R, Rich W, Heldt G, Leone T, Finer NN. Tidal volume threshold for colorimetric carbon dioxide detectors available for use in neonates. Pediatrics 2008;121:e1524–7. 216. Morley CJ, Davis PG, Doyle LW, Brion LP, Hascoet JM, Carlin JB. Nasal CPAP or intubation at birth for very preterm infants. N Engl J Med 2008;358:700–8. 217. Network SSGotEKSNNR, Finer NN, Carlo WA, et al. Early CPAP versus surfactant in extremely preterm infants. N Engl J Med 2010;362:1970–9. 218. Dunn MS, Kaempf J, de Klerk A, et al. Randomized trial comparing 3 approaches to the initial respiratory management of preterm neonates. Pediatrics 2011;128:e1069–76. 219. Hishikawa K, Goishi K, Fujiwara T, Kaneshige M, Ito Y, Sago H. Pulmonary air leak associated with CPAP at term birth resuscitation. Arch Dis Child Fetal Neonatal Ed 2015, pii: fetalneonatal-2014-307891. 220. Poets CF, Rudiger M. Mask CPAP during neonatal transition: too much of a good thing for some term infants? Arch Dis Child Fetal Neonatal Ed 2015, pii: fetalneonatal-2015-308236. 221. Houri PK, Frank LR, Menegazzi JJ, Taylor R. A randomized, controlled trial of two-thumb vs two-finger chest compression in a swine infant model of cardiac arrest [see comment]. Prehosp Emerg Care: Off J Natl Assoc EMS Phys Natl Assoc State EMS Dir 1997;1:65–7. 222. David R. Closed chest cardiac massage in the newborn infant. Pediatrics 1988;81:552–4. 223. Menegazzi JJ, Auble TE, Nicklas KA, Hosack GM, Rack L, Goode JS. Two-thumb versus two-finger chest compression during CRP in a swine infant model of cardiac arrest. Ann Emerg Med 1993;22:240–3. 224. Thaler MM, Stobie GH. An improved technique of external caridac compression in infants and young children. N Engl J Med 1963;269:606–10. 225. Christman C, Hemway RJ, Wyckoff MH, Perlman JM. The two-thumb is superior to the two-finger method for administering chest compressions in a manikin model of neonatal resuscitation. Arch Dis Child Fetal Neonatal Ed 2011;96:F99–101. 226. Dellimore K, Heunis S, Gohier F, et al. Development of a diagnostic glove for unobtrusive measurement of chest compression force and depth during neonatal CPR. Conf Proc IEEE Eng Med Biol Soc 2013;2013: 350–3. 227. Dorfsman ML, Menegazzi JJ, Wadas RJ, Auble TE. Two-thumb vs twofinger chest compression in an infant model of prolonged cardiopulmonary resuscitation. Acad Emerg Med: Off J Soc Acad Emerg Med 2000;7: 1077–82. 228. Martin PS, Kemp AM, Theobald PS, Maguire SA, Jones MD. Do chest compressions during simulated infant CPR comply with international recommendations? Arch Dis Child 2013;98:576–81. 229. Martin P, Theobald P, Kemp A, Maguire S, Maconochie I, Jones M. Real-time feedback can improve infant manikin cardiopulmonary resuscitation by up to 79%—a randomised controlled trial. Resuscitation 2013;84:1125–30. 230. Moya F, James LS, Burnard ED, Hanks EC. Cardiac massage in the newborn infant through the intact chest. Am J Obstet Gynecol 1962;84:798–803. 231. Park J, Yoon C, Lee JC, et al. Manikin-integrated digital measuring system for assessment of infant cardiopulmonary resuscitation techniques. IEEE J Biomed Health Inf 2014;18:1659–67. 232. Todres ID, Rogers MC. Methods of external cardiac massage in the newborn infant. J Pediatr 1975;86:781–2. 233. Udassi S, Udassi JP, Lamb MA, et al. Two-thumb technique is superior to two-finger technique during lone rescuer infant manikin CPR. Resuscitation 2010;81:712–7. 234. Whitelaw CC, Slywka B, Goldsmith LJ. Comparison of a two-finger versus twothumb method for chest compressions by healthcare providers in an infant mechanical model. Resuscitation 2000;43:213–6. 235. Lim JS, Cho Y, Ryu S, et al. Comparison of overlapping (OP) and adjacent thumb positions (AP) for cardiac compressions using the encircling method in infants. Emerg Med J: EMJ 2013;30:139–42. 236. Orlowski JP. Optimum position for external cardiac compression in infants and young children. Ann Emerg Med 1986;15:667–73. 237. Phillips GW, Zideman DA. Relation of infant heart to sternum: its significance in cardiopulmonary resuscitation. Lancet 1986;1:1024–5. 238. Saini SS, Gupta N, Kumar P, Bhalla AK, Kaur H. A comparison of two-fingers technique and two-thumbs encircling hands technique of chest compression in neonates. J Perinatol: Off J California Perinat Assoc 2012;32:690–4. 239. You Y. Optimum location for chest compressions during two-rescuer infant cardiopulmonary resuscitation. Resuscitation 2009;80:1378–81. 240. Meyer A, Nadkarni V, Pollock A, et al. Evaluation of the Neonatal Resuscitation Program’s recommended chest compression depth using computerized tomography imaging. Resuscitation 2010;81:544–8. 241. Dannevig I, Solevag AL, Saugstad OD, Nakstad B. Lung injury in asphyxiated newborn pigs resuscitated from cardiac arrest—the impact of supplementary oxygen, longer ventilation intervals and chest compressions at different compression-to-ventilation ratios. Open Respir Med J 2012;6:89–96. 242. Dannevig I, Solevag AL, Sonerud T, Saugstad OD, Nakstad B. Brain inflammation induced by severe asphyxia in newborn pigs and the impact of alternative resuscitation strategies on the newborn central nervous system. Pediatr Res 2013;73:163–70. 243. Hemway RJ, Christman C, Perlman J. The 3:1 is superior to a 15:2 ratio in a newborn manikin model in terms of quality of chest compressions and number of ventilations. Arch Dis Child Fetal Neonatal Ed 2013;98:F42–5. 244. Solevag AL, Dannevig I, Wyckoff M, Saugstad OD, Nakstad B. Extended series of cardiac compressions during CPR in a swine model of perinatal asphyxia. Resuscitation 2010;81:1571–6. 245. Solevag AL, Dannevig I, Wyckoff M, Saugstad OD, Nakstad B. Return of spontaneous circulation with a compression:ventilation ratio of 15:2 versus 3:1 in newborn pigs with cardiac arrest due to asphyxia. Arch Dis Child Fetal Neonatal Ed 2011;96:F417–21. 246. Solevag AL, Madland JM, Gjaerum E, Nakstad B. Minute ventilation at different compression to ventilation ratios, different ventilation rates, and continuous chest compressions with asynchronous ventilation in a newborn manikin. Scand J Trauma Resuscitation Emerg Med 2012;20:73. 247. Dean JM, Koehler RC, Schleien CL, et al. Improved blood flow during prolonged cardiopulmonary resuscitation with 30% duty cycle in infant pigs. Circulation 1991;84:896–904. 248. Berkowitz ID, Chantarojanasiri T, Koehler RC, et al. Blood flow during cardiopulmonary resuscitation with simultaneous compression and ventilation in infant pigs. Pediatr Res 1989;26:558–64. 249. Linner R, Werner O, Perez-de-Sa V, Cunha-Goncalves D. Circulatory recovery is as fast with air ventilation as with 100% oxygen after asphyxia-induced cardiac arrest in piglets. Pediatr Res 2009;66:391–4. 250. Lipinski CA, Hicks SD, Callaway CW. Normoxic ventilation during resuscitation and outcome from asphyxial cardiac arrest in rats. Resuscitation 1999;42:221–9. 251. Perez-de-Sa V, Cunha-Goncalves D, Nordh A, et al. High brain tissue oxygen tension during ventilation with 100% oxygen after fetal asphyxia in newborn sheep. Pediatr Res 2009;65:57–61. 252. Solevag AL, Dannevig I, Nakstad B, Saugstad OD. Resuscitation of severely asphyctic newborn pigs with cardiac arrest by using 21% or 100% oxygen. Neonatology 2010;98:64–72. 253. Temesvari P, Karg E, Bodi I, et al. Impaired early neurologic outcome in newborn piglets reoxygenated with 100% oxygen compared with room air after pneumothorax-induced asphyxia. Pediatr Res 2001;49:812–9. 254. Walson KH, Tang M, Glumac A, et al. Normoxic versus hyperoxic resuscitation in pediatric asphyxial cardiac arrest: effects on oxidative stress. Crit Care Med 2011;39:335–43. J. Wyllie et al. / Resuscitation 95 (2015) 249–263 263 255. Yeh ST, Cawley RJ, Aune SE, Angelos MG. Oxygen requirement during cardiopulmonary resuscitation (CPR) to effect return of spontaneous circulation. Resuscitation 2009;80:951–5. 256. Berg RA, Henry C, Otto CW, et al. Initial end-tidal CO2 is markedly elevated during cardiopulmonary resuscitation after asphyxial cardiac arrest. Pediatr Emerg Care 1996;12:245–8. 257. Bhende MS, Karasic DG, Menegazzi JJ. Evaluation of an end-tidal CO2 detector during cardiopulmonary resuscitation in a canine model for pediatric cardiac arrest. Pediatr Emerg Care 1995;11:365–8. 258. Bhende MS, Thompson AE. Evaluation of an end-tidal CO2 detector during pediatric cardiopulmonary resuscitation. Pediatrics 1995;95:395–9. 259. Bhende MS, Karasic DG, Karasic RB. End-tidal carbon dioxide changes during cardiopulmonary resuscitation after experimental asphyxial cardiac arrest. Am J Emerg Med 1996;14:349–50. 260. Chalak LF, Barber CA, Hynan L, Garcia D, Christie L, Wyckoff MH. End-tidal CO(2) detection of an audible heart rate during neonatal cardiopulmonary resuscitation after asystole in asphyxiated piglets. Pediatr Res 2011;69:401–5. 261. Crespo SG, Schoffstall JM, Fuhs LR, Spivey WH. Comparison of two doses of endotracheal epinephrine in a cardiac arrest model. Ann Emerg Med 1991;20:230–4. 262. Jasani MS, Nadkarni VM, Finkelstein MS, Mandell GA, Salzman SK, Norman ME. Effects of different techniques of endotracheal epinephrine administration in pediatric porcine hypoxic-hypercarbic cardiopulmonary arrest. Crit Care Med 1994;22:1174–80. 263. Mielke LL, Frank C, Lanzinger MJ, et al. Plasma catecholamine levels following tracheal and intravenous epinephrine administration in swine. Resuscitation 1998;36:187–92. 264. Roberts JR, Greenberg MI, Knaub MA, Kendrick ZV, Baskin SI. Blood levels following intravenous and endotracheal epinephrine administration. JACEP 1979;8:53–6. 265. Hornchen U, Schuttler J, Stoeckel H, Eichelkraut W, Hahn N. Endobronchial instillation of epinephrine during cardiopulmonary resuscitation. Crit Care Med 1987;15:1037–9. 266. Wyckoff MH, Perlman JM, Laptook AR. Use of volume expansion during delivery room resuscitation in near-term and term infants. Pediatrics 2005;115:950–5. 267. Harrington DJ, Redman CW, Moulden M, Greenwood CE. The long-term outcome in surviving infants with Apgar zero at 10 minutes: a systematic review of the literature and hospital-based cohort. Am J Obstet Gynecol 2007;196:e1–5. 268. Lee SK, Penner PL, Cox M. Comparison of the attitudes of health care professionals and parents toward active treatment of very low birth weight infants. Pediatrics 1991;88:110–4. 269. Kopelman LM, Irons TG, Kopelman AE. Neonatologists judge the “Baby Doe” regulations. N Engl J Med 1988;318:677–83. 270. Sanders MR, Donohue PK, Oberdorf MA, Rosenkrantz TS, Allen MC. Perceptions of the limit of viability: neonatologists’ attitudes toward extremely preterm infants. J Perinatol: Off J California Perinat Assoc 1995;15:494–502. 271. Rysavy MA, Li L, Bell EF, et al. Between-hospital variation in treatment and outcomes in extremely preterm infants. N Engl J Med 2015;372:1801–11. 272. Patel H, Beeby PJ. Resuscitation beyond 10 minutes of term babies born without signs of life. J Paediatr Child Health 2004;40:136–8. 273. Casalaz DM, Marlow N, Speidel BD. Outcome of resuscitation following unexpected apparent stillbirth. Arch Dis Child Fetal Neonatal Ed 1998;78. F112-F5. 274. Kasdorf E, Laptook A, Azzopardi D, Jacobs S, Perlman JM. Improving infant outcome with a 10 min Apgar of 0. Arch Dis Child Fetal Neonatal Ed 2015;100:F102–5. 275. Laptook AR, Shankaran S, Ambalavanan N, et al. Outcome of term infants using apgar scores at 10 minutes following hypoxic-ischemic encephalopathy. Pediatrics 2009;124:1619–26. 276. Sarkar S, Bhagat I, Dechert RE, Barks JD. Predicting death despite therapeutic hypothermia in infants with hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed 2010;95:F423–8. 277. Bottoms SF, Paul RH, Mercer BM, et al. Obstetric determinants of neonatal survival: antenatal predictors of neonatal survival and morbidity in extremely low birth weight infants. Am J Obstet Gynecol 1999;180:665–9. 278. Ambalavanan N, Carlo WA, Bobashev G, et al. Prediction of death for extremely low birth weight neonates. Pediatrics 2005;116:1367–73. 279. Manktelow BN, Seaton SE, Field DJ, Draper ES. Population-based estimates of in-unit survival for very preterm infants. Pediatrics 2013;131:e425–32. 280. Medlock S, Ravelli AC, Tamminga P, Mol BW, Abu-Hanna A. Prediction of mortality in very premature infants: a systematic review of prediction models. PloS One 2011;6:e23441. 281. Tyson JE, Parikh NA, Langer J, et al. Intensive care for extreme prematurity—moving beyond gestational age. N Engl J Med 2008;358:1672–81. 282. Marlow N, Bennett C, Draper ES, Hennessy EM, Morgan AS, Costeloe KL. Perinatal outcomes for extremely preterm babies in relation to place of birth in England: the EPICure 2 study. Arch Dis Child Fetal Neonatal Ed 2014;99:F181–8. 283. Nuffield Council on Bioethics. Critical care decisions in fetal and neonatal medicine: ethical issues. 2006 ISBN 1 904384 14. 284. Swamy R, Mohapatra S, Bythell M, Embleton ND. Survival in infants live born at less than 24 weeks’ gestation: the hidden morbidity of non-survivors. Arch Dis Child Fetal Neonatal Ed 2010;95:F293–4. 285. Baskett PJ, Steen PA, Bossaert L. European Resuscitation Council guidelines for resuscitation 2005 Section 8. The ethics of resuscitation and end-of-life decisions. Resuscitation 2005;67:S171–80 [Suppl 1]. 286. Fulbrook P, Latour J, Albarran J, et al. The presence of family members during cardiopulmonary resuscitation: European federation of Critical Care Nursing associations. European Society of Paediatric and Neonatal Intensive Care and European Society of Cardiology Council on Cardiovascular Nursing and Allied Professions Joint Position Statement. Eur J Cardiovasc Nurs 2007;6:255–8. 287. Brambrink AM, Ichord RN, Martin LJ, Koehler RC, Traystman RJ. Poor outcome after hypoxia-ischemia in newborns is associated with physiological abnormalities during early recovery. Possible relevance to secondary brain injury after head trauma in infants. Exp Toxicol Pathol 1999;51:151–62. 288. Vannucci RC, Vannucci SJ. Cerebral carbohydrate metabolism during hypoglycemia and anoxia in newborn rats. Ann Neurol 1978;4:73–9. 289. Yager JY, Heitjan DF, Towfighi J, Vannucci RC. Effect of insulin-induced and fasting hypoglycemia on perinatal hypoxic-ischemic brain damage. Pediatr Res 1992;31:138–42. 290. Salhab WA, Wyckoff MH, Laptook AR, Perlman JM. Initial hypoglycemia and neonatal brain injury in term infants with severe fetal acidemia. Pediatrics 2004;114:361–6. 291. Kent TA, Soukup VM, Fabian RH. Heterogeneity affecting outcome from acute stroke therapy: making reperfusion worse. Stroke 2001;32:2318–27. 292. Srinivasan V, Spinella PC, Drott HR, Roth CL, Helfaer MA, Nadkarni V. Association of timing, duration, and intensity of hyperglycemia with intensive care unit mortality in critically ill children. Pediatr Crit Care Med: J Soc Crit Care Med World Federation Pediatric Intensive Crit Care Soc 2004;5:329–36. 293. Klein GW, Hojsak JM, Schmeidler J, Rapaport R. Hyperglycemia and outcome in the pediatric intensive care unit. J Pediatr 2008;153:379–84. 294. LeBlanc MH, Huang M, Patel D, Smith EE, Devidas M. Glucose given after hypoxic ischemia does not affect brain injury in piglets. Stroke 1994;25:1443–7 [discussion 8]. 295. Hattori H, Wasterlain CG. Posthypoxic glucose supplement reduces hypoxicischemic brain damage in the neonatal rat. Ann Neurol 1990;28:122–8. 296. Edwards AD, Brocklehurst P, Gunn AJ, et al. Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data. BMJ 2010;340:c363. 297. Gluckman PD, Wyatt JS, Azzopardi D, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 2005;365:663–70. 298. Shankaran S, Laptook AR, Ehrenkranz RA, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 2005;353:1574–84. 299. Azzopardi DV, Strohm B, Edwards AD, et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med 2009;361:1349–58. 300. Eicher DJ, Wagner CL, Katikaneni LP, et al. Moderate hypothermia in neonatal encephalopathy: efficacy outcomes. Pediatr Neurol 2005;32:11–7. 301. Azzopardi D, Strohm B, Marlow N, et al. Effects of hypothermia for perinatal asphyxia on childhood outcomes. N Engl J Med 2014;371:140–9. 302. Iliodromiti S, Mackay DF, Smith GC, Pell JP, Nelson SM. Apgar score and the risk of cause-specific infant mortality: a population-based cohort study. Lancet 2014;384:1749–55. 303. Rudiger M, Braun N, Aranda J, et al. Neonatal assessment in the delivery room—Trial to Evaluate a Specified Type of Apgar (TEST-Apgar). BMC Pediatr 2015;15:18. 304. Dalili H, Nili F, Sheikh M, Hardani AK, Shariat M, Nayeri F. Comparison of the four proposed Apgar scoring systems in the assessment of birth asphyxia and adverse early neurologic outcomes. PloS One 2015;10:e0122116. 305. Savoldelli GL, Naik VN, Park J, Joo HS, Chow R, Hamstra SJ. Value of debriefing during simulated crisis management: oral versus video-assisted oral feedback. Anesthesiology 2006;105:279–85. 306. Edelson DP, Litzinger B, Arora V, et al. Improving in-hospital cardiac arrest process and outcomes with performance debriefing. Arch Intern Med 2008;168:1063–9. 307. DeVita MA, Schaefer J, Lutz J, Wang H, Dongilli T. Improving medical emergency team (MET) performance using a novel curriculum and a computerized human patient simulator. Qual Saf Health Care 2005;14:326–31. 308. Wayne DB, Butter J, Siddall VJ, et al. Simulation-based training of internal medicine residents in advanced cardiac life support protocols: a randomized trial. Teach Learn Med 2005;17:210–6. 309. Clay AS, Que L, Petrusa ER, Sebastian M, Govert J. Debriefing in the intensive care unit: a feedback tool to facilitate bedside teaching. Crit Care Med 2007;35:738–54. 310. Blum RH, Raemer DB, Carroll JS, Dufresne RL, Cooper JB. A method for measuring the effectiveness of simulation-based team training for improving communication skills. Anesth Analg 2005;100:1375–80 [table of contents]. 311. Rudiger M, Braun N, Gurth H, Bergert R, Dinger J. Preterm resuscitation I: clinical approaches to improve management in delivery room. Early Hum Dev 2011;87:749–53. 312. Schmid MB, Reister F, Mayer B, Hopfner RJ, Fuchs H, Hummler HD. Prospective risk factor monitoring reduces intracranial hemorrhage rates in preterm infants. Dtsch Arzteblatt Int 2013;110:489–96.