Pediatric resuscitation Thomas Nicolai University Children’s Hospital, Dr v Haunersches Kinderspital, Munich, Germany Correspondence to Professor T. Nicolai, Univ Kinderklinik Mu¨nchen, Lindwurmstr 4, 80337 Mu¨nchen, Germany Tel: +49 89 5160 2811; fax: +49 89 5160 4408; e-mail: [email protected]

Current Opinion in Anesthesiology 2008, 21:204–208

Purpose of review The new International Liaison Committee on Resuscitation documents, published in 2005, include important changes in pediatric resuscitation. Some issues that were left pending have since been supplemented with new studies. Their impact will be discussed here. Recent findings Studies on oxygen use for neonatal resuscitation have consistently found room air to be superior to 100% oxygen. Prospective studies indicate that intubation by first responders in preclinical resuscitation of children is dangerous and should probably be avoided. New studies point to a better neurological outcome with hypothermia in neurologically depressed neonates after perinatal asphyxia. Summary Resuscitation of ‘depressed’ near-term neonates should be started with an oxygen content of less than 100%, and only change to 100% if the child remains bradycardic and cyanotic. A neonate who can be resuscitated with room air will receive no benefit from 100% oxygen and may even have a worse outcome. If the first responder in a pediatric emergency is out of training with pediatric intubation he or she should feel reassured that resuscitation without an attempt at endotracheal intubation is acceptable. Presently, hypothermia in neonates after birth asphyxia should be used within controlled studies, or at least follow the protocols of published studies and be performed in specialized centers. Keywords airway management, hypothermia, neonate asphyxia, resuscitation, room air Curr Opin Anesthesiol 21:204–208 ß 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins 0952-7907

Introduction The new recommendations of the International Liaison Committee on Resuscitation, published in 2005 [1], include a number of changes in pediatric resuscitation. Unfortunately but inevitably many of the recommendations are derived by extrapolation from adult data or from the analysis of manikin studies. The extension of adult data and experience into childhood is always limited by the basic difference in physiology (particularly in neonates), and the different pathophysiology leading to cardiocirculatory arrest in children. Some of the issues that were left pending in the new guidelines have since been discussed further and supplemented with new studies and data.

Neonatal resuscitation Some form of resuscitation will be required in 5–10% of newborns [2]. Neonates have a most radically different physiological setup to adults. Not only is the prenatal circulation entirely different from an adult’s, but a switch

back to it (with persistent pulmonary hypertension) can happen during hypoxia or postnatal distress. In addition, normal values of physiological parameters in healthy neonates differ greatly from those familiar to medical professionals caring for adults. In particular, the arterial oxygen saturation in healthy neonates is only around 70–90% in the first 10 min after birth, without causing hypoxic organ damage [3,4]. In addition, the high avidity of fetal hemoglobin for oxygen will require even lower oxygen partial pressures to achieve the same saturation compared with adult-type hemoglobin. Clinical experience and study data suggest that the neonate has a unique ability to adapt to low tissue oxygen content without permanent damage. Conversely, new studies suggest that neonates may have a diminished ability to detoxify oxygen radicals that are created in the presence of higher than ambient partial pressures of oxygen [5,6]. Brain perfusion seems to be altered over prolonged periods after even a brief exposure to 100% oxygen [7]. Oxygen toxicity is even more of concern in premature neonates, where retinopathy can be

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caused by brief periods of hyperoxia, and can lead to blindness [8]. Studies on oxygen use for neonatal resuscitation have been recently summarized in meta-analyses, and these have consistently found that neonates resuscitated with 100% oxygen fare worse in terms of mortality (first week, neonatal period and later) and morbidity compared to those resuscitated with room air [9,10]. These findings seem to go against the grain of the adult experience and the instincts of most medical first responders. The studies come from less developed countries, where prenatal and postnatal care have fewer resources to draw on, and it is therefore not entirely clear whether the results can really be translated directly to the situation in more developed countries. For example, co-interventions with antenatal steroids, surfactant, etc. were less frequently available than would be expected in more developed healthcare systems and might change the effects of this treatment (no oxygen) on mortality. The availability of supplemental oxygen and its impact on mortality was not addressed. A meta-analysis found that 174 of the 177 reported deaths in these studies had occurred in developing countries [11]. In addition, most infants included were not severely asphyctic but rather suffered from mild to moderate cardiorespiratory depression [10]. Although no changes have yet been made to most official guidelines [1,2,12], the effect on mortality and morbidity observed in these studies is substantial. Therefore, many neonatologists today recommend starting resuscitation in ‘depressed’ near-term neonates with room air or an oxygen content of less than 100% and only change to 100% if the child remains bradycardic and cyanotic, for example after 90 s [13,14].

Despite the trend towards a more cautious use of supplementary oxygen in neonates, adequate ventilation itself is crucial: hypoventilation can lead to a return to prenatal circulatory conditions, leaving the child deeply hypoxic and unresponsive to ventilatory efforts [15]. Intubation is not the only and actually not even the preferred form of airway management in neonates. Usually mask-bag ventilation will be sufficient but other avenues are available if this is difficult or impossible [1]. Pharyngeal ventilation with an endotracheal tube advanced through the nose into the pharynx has become widespread practice in many centers and avoids the risks of intubation [16]. Similarly, laryngeal mask airways may be used in difficult neonatal airway conditions, such as mandibular hypoplasia and glossoptosis, for example in Pierre Robin and other facial dysplasia syndromes, by persons trained in their use [1]. This syndrome and its variants used to be the bane of neonatal airway management, but use of a laryngeal mask usually allows avoidance of disastrous situations in which the infant cannot be intubated or ventilated [17]. It was initially thought that these syndromes encompass some degree of diminished intelligence until it became clear that good airway management with the avoidance of severe hypoxia leads to completely normal development in these patients.

Preclinical airway management

It seems prudent to aim for lower oxygen saturations in neonates than in older children and adults, and to reduce oxygen (if used) as soon as the arterial oxygen saturation (SaO2) reaches the physiological range – between 88 and 93% – although no evidence is available as to which level of saturation is optimal. Several large clinical studies are underway to determine the physiological or desirable saturation values in neonates and premature infants. It remains unclear whether children with an increased risk for pulmonary hypertension (meconium aspiration, sepsis, etc.) would benefit from a more liberal use of oxygen [10,13].

The preclinical airway management of children is a source of considerable anxiety and preoccupation for first responders. Mask-bag ventilation or the use of laryngeal mask airways by healthcare providers experienced in their use are as effective as intubation [18–20]. Recently, some emergency medical institutions considered enabling first responders to intubate children. A remarkable study assessed this approach in a prospective fashion [18]. It was concluded that even after training of all emergency medical personnel, the institution of a policy to intubate all children who required respiratory assistance did not improve the survival of children, and an unacceptable number of complications arose from this procedure. Failed intubations and tube dislocations contributed to fatal outcomes. Only 52% of the patients in whom it was intended were successfully intubated. This seems to indicate that intubation in the preclinical resuscitation of children is dangerous and should probably be avoided.

Few data are available regarding the use of room air in the resuscitation of premature infants [10]. If these children suffer from severe surfactant deficiency, they may not be able to achieve sufficient oxygenation without supplemental oxygen. Upper limits of oxygen saturation should, however, be set conservatively (e.g. <94%) and monitored continuously to minimize the risk of retinopathy.

However, several specific points of this study need to be taken into account. First, the emergency personnel were trained with the help of pediatric manikins only. Second, all intubations were performed without the use of sedation, anesthetic or relaxants. This may explain in part the high failure rate. Also, it is not clear whether these results pertain to medical emergency systems that are structured

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206 Resuscitation and trauma anesthesia

differently and employ doctors on site, usually welltrained anesthetists with ample daily intubation practice [21,22]. Beyond these caveats, there are important lessons to be learned from this study: First, intubation should only be attempted when the person performing it has experience and feels secure with this procedure. Second, it is acceptable and probably as effective for people who are not trained in pediatric intubation to use mask-bag ventilation, or other forms of airway assistance (laryngeal masks, pharyngeal ventilation, etc.) [23]. The recent change in recommendations away from intratracheal delivery of resuscitation drugs towards the use of intraosseous access needles removes another argument for mandatory endotracheal intubation [1,24]. Another change in the guidelines concerns the use of cuffed endotracheal tubes in children. They are now acceptable as long as the cuff pressure is measured and adjusted to <20 cmH2O [25]. In our experience, however, they are not really needed and may even be more difficult to place in an emergent situation. Hyperventilation during and after resuscitation should be avoided, as a resulting elevated intrathoracic pressure may impede circulation [26] and low CO2 may diminish brain blood flow, at least if the cerebral autoregulation is intact.

Assessment of circulation The detection of the presence or absence of a circulation in children during resuscitation is difficult [27,28]. A recent study found that feeling for the pulse or observing umbilical pulsations in neonates yielded an extremely high rate of false negatives; that is, the observers did not note signs of circulation when in reality the heart rate was completely normal [28]. It is therefore useful, at least for nonprofessionals, that the attempt to detect the pulse has been removed from current guidelines and replaced by the search for other life signs [1].

Chest compressions Extending data gleaned from adult resuscitation into the pediatric field, the ventilation/compression rates have been changed for children. It has been found from manikin studies that even when 100 chest compressions per minute were aimed at, the real number achieved with a 15 : 2 ratio was usually only around 60 [29,30]. This is the lowest limit of a regular heart rate for a sufficient cardiac output to maintain coronary perfusion in infants. From this observation it appears likely that future recommendations might actually aim at even faster rhythms. It has been found that the two-thumb method in infants is more effective than the two-finger-method in a manikin study [31]. However, it has also been noted in this study

that an alarmingly large proportion of chest compressions were ineffective, regardless of the method. Despite the recent focus on the number of chest compressions necessary to achieve sufficient diastolic aortic filling pressures for coronary perfusion, we need to remember that pediatric resuscitation usually becomes necessary after a primarily hypoxic event due to respiratory problems. Therefore, effective ventilation alone may be all that is needed, and an existing (but difficult-to-detect) residual circulation may then become effective and notable.

Obstruction by a foreign body A change has been made to the recommendations concerning obstruction of the airway by a foreign body, with suffocation [1]. On these rare occasions, artificial coughs created by the Heimlich maneuver are recommended for older children, as they were before. It has become clear, however, that particularly in infants with their unprotected large abdominal organs this procedure has led to an unacceptable number of complications, including organ rupture. Therefore, as in cardiopulmonary resuscitation, only chest compressions are recommended for infants (after back blows). Scandinavian studies have found that chest compressions will yield expulsion pressures against the closed airway that are as effective as the Heimlich maneuver [32]. It may be that in the future thoracic chest compressions will generally replace the Heimlich maneuver to simplify training. However, in the light of the successful use of the Heimlich maneuver in the past this change has not been made as yet.

Defibrillation The use of defibrillators has been simplified with the new rules switching from a stacked dose to a single shock and recommending half the dose for biphasic defibrillators in adults. For children, the same dose is recommended for biphasic and monophasic defibrillation, and automatic defibrillators can be used (preferably with pediatric pedals) down to the age of 1 year. However, ventricular fibrillation is a rather unusual rhythm during pediatric resuscitation (below 10%). If present, the patients will either have preexisting cardiac disease (e.g. congenital cardiac defects) or congenital rhythm disturbances such as Romano–Ward syndrome. Most children display asystole during resuscitation [1].

Hypothermia after resuscitation The biological plausibility of this approach comes from animal experiments and patient data showing decreased

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Pediatric resuscitation Nicolai 207

oxidative stress markers and neural apoptosis [33–40] with hypothermia after a hypoxic event. In observed sudden cardiac collapse and quickly instituted resuscitative efforts hypothermia leads to an improved neurological outcome in adults [41,42]. This situation is only rarely found in children, and the value of postresuscitation hypothermia in other scenarios is unknown. Many (but not all) neonates with moderately severe birth asphyxia recover surprisingly well without specific treatment. However, some new studies point to a better neurological outcome when hypothermia is used in children who remain neurologically depressed after resuscitation [43–46]. All studies were unblinded and significant only for the composite outcome variable of death or neurological damage, whereas mortality was not improved. The neurological assessment has been criticized as being made at too early an age. The individual likelihood of a significant benefit for each new child from this treatment is not large due to statistical insecurity in the available studies [47]. Children with the most severe changes in EEG as well as those with relatively mild changes after asphyxia had no benefit from hypothermia. It seems that children with a moderately severe EEG pattern of damage will be the group that may have an improved outcome with hypothermia. A newer large trial found similar benefits after neonatal asphyxia without stratifying for EEG changes [48]. As it is not easy to implement this therapy safely in neonates worldwide, and induced hypothermia may have a number of relevant side effects (including arrhythmias) [49–52], no general recommendation to use this treatment has yet been made. It has been suggested to limit this treatment to controlled studies at the moment. Still, some publications have proposed using hypothermia in children who remain comatose after an asphyctic event even without new guidelines [14] and this may be what the parents wish when faced with the prospect of possible neurological sequelae after an asphyctic event at birth. As neonatal EEGs will not be available in every delivery room, patients who might benefit could in practice be identified according to criteria such as the ones recently proposed [48]: that is, neonates with a gestational age of more than 35 weeks who remain lethargic or comatose and display periodic breathing or apnoea, have an APGAR score of less than 6 after 10 min, and still who require ventilation at this time. Children weighing less than 2000 g as well as those older than 6 h at the time of decision are excluded. In practice, this is a rather demanding therapy and eligible children should therefore be transferred to a center specialized in this procedure.

Conclusion The new recommendations for pediatric resuscitation include a change in the ventilation/compression rates extrapolated from adult data down to 1 year of age, and allow the use of automated defibrillators down to this age. Controversial discussions concern the use of room air for neonatal resuscitation and hypothermia after birth asphyxia. Solid new data support the former in specific circumstances, although its applicability outside developing countries and moderately depressed neonates is presently unknown. Hypothermia after birth asphyxia may open a new therapeutic modality in children who remain neurologically depressed after birth asphyxia, although it should be used only within controlled studies, or should follow the protocols of published studies, and is best performed in specialized centers.

References and recommended reading Papers of particular interest, published within the annual period of review, have been highlighted as:  of special interest  of outstanding interest Additional references related to this topic can also be found in the Current World Literature section in this issue (pp. 256–257). 1

International Liaison Committee on Resuscitation (ILCOR). Guidelines for pediatric cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2005; 112:167–187.

2

Niermeyer S, Kattwinkel P, Van Reempts et al. International Guidelines for Neonatal Resuscitation: an excerpt from the Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care: International Consensus on Science. Pediatrics 2000; 106:e29.

3

Saugstad OD. Oxygen saturations immediately after birth. J Pediatr 2006; 148:569–570.

4

Rabi Y, Yee W, Chen SY, Singhal N. Oxygen saturation trends immediately after birth. J Pediatr 2006; 148:590–594.

5

Vento M, Asensi M, Sastre J, et al. Resuscitation with room air instead of 100% oxygen prevents oxidative stress in moderately asphyxiated term neonates. Pediatrics 2001; 107:642–647.

6

Vento M, Asensi M, Sastre M, et al. Oxidative stress in asphyxiated term infants resuscitated with 100% oxygen. J Pediatr 2003; 142:240–246.

7

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–F86.

8

Tin W, Milligan DWA, Pennefather P, Hey E. Pulse oximetry, severe retinopathy and outcome at one year in babies of less than 28 weeks gestation. Arch Dis Child Fetal Neonatal Ed 2001; 84:F106–F110.

9

Tan A, Schulze A, O’Donnell CP, Davis PG. Air versus oxygen for resuscitation of infants at birth. Cochrane Database Syst Rev 2005; 1:CD002273.

10 Rabi Y, Rabi D, Yee W. Room air resuscitation of the depressed newborn:  a systematic review and meta-analysis. Resuscitation 2007; 72:353–363. This is an in-depth meta-analysis of studies comparing oxygen and room air for neonatal resuscitation, detailing their strengths and deficiencies. 11 Richmond S, Goldsmith JP. Air or 100% oxygen in neonatal resuscitation? Clin Perinatol 2006; 33:11–27. 12 Kattwinkel J, Niermeyer S, Nadkarni V, et al. An Advisory Statement From the Pediatric Working Group of the International Liaison Committee on Resuscitation. Pediatrics 1999; 103:e56. 13 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; 364:1329–1333. 14 Hansmann G, Humpl T, Zimmermann A, Buhrer C, et al. ILCOR’s new resuscitation guidelines in preterm and term infants: critical discussion and suggestions for implementation. Klin Padiatr 2007; 219:50–57. 15 Hernandez-Diaz S, Van Marter LJ, Werler MM, et al. Risk factors for persistent pulmonary hypertension of the newborn. Pediatrics 2007; 120:e272–e282.

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

208 Resuscitation and trauma anesthesia 16 Lindner W, Pohlandt F. Oxygenation and ventilation in spontaneously breath ing very preterm infants with nasopharyngeal CPAP in the delivery room. Acta Paediatr 2007; 96:17–22. This paper provides data on the efficacy of noninvasive ventilation in neonates. 17 Wagener S, Rayatt SS, Tatman AJ, et al. Management of infants with Pierre Robin sequence. Cleft Palate Craniofac J 2003; 40:180–185. 18 Gausche M, Lewis RJ, Stratton SJ, et al. Effect of out-of-hospital pediatric endotracheal intubation on survival and neurological outcome: a controlled clinical trial. JAMA 2000; 283:783–790. 19 Stockinger ZT, McSwain NE Jr. Prehospital endotracheal intubation for trauma does not improve survival over bag-valve-mask ventilation. J Trauma 2004; 56:531–536.

34 Busto R, Globus MY, Dietrich WD, et al. Effect of mild hypothermia onischemia-induced release of neurotransmitters and free fatty acids in rat brain. Stroke 1989; 20:904–910. 35 Nakashima K, Todd MM. Effects of hypothermia on the rate of excitatory amino acid release after ischemic depolarization. Stroke 1996; 27:913–918. 36 Globus MY, Alonso O, Dietrich WD, et al. Glutamate release and free radical production following brain injury: effects of posttraumatic hypothermia. J Neurochem 1995; 65:1704–1711. 37 Edwards AD, Yue X, Squier MV, et al. Specific inhibition of apoptosis after cerebral hypoxia-ischaemia by moderate postinsult hypothermia. Biochem Biophys Res Commun 1995; 217:1193–1199.

20 Park C, Bahk JH, Ahn WS, et al. The laryngeal mask airway in infants and children. Can J Anaesth 2001; 48:413–417.

38 Xu L, Yenari MA, Steinberg GK, et al. Mild hypothermia reduces apoptosis of mouse neurons in vitro early in the cascade. J Cereb Blood Flow Metab 2002; 22:21–28.

21 Timmermann A, Russo SG, Eich C, et al. The out-of-hospital esophageal and endobronchial intubations performed by emergency physicians. Anesth Analg 2007; 104:619–623.

39 Zhu C, Wang X, Cheng X, et al. Postischemic hypothermia-induced tissue protection and diminished apoptosis after neonatal cerebral hypoxiaischemia. Brain Res 2004; 996:67–75.

22 Schmidt U, Geerling J, Fuhler M, et al. Pediatric prehospital trauma care. A retrospective comparison of air and ground transportation. Unfallchirurg 2002; 105:1000–1006.

40 Akisu M, Huseyinov A, Yalaz M, et al. Selective head cooling with hypothermia suppresses the generation of platelet-activating factor in cerebrospinal fluid of newborn infants with perinatal asphyxia. Prostaglandins Leukot Essent Fatty Acids 2003; 69:45–50.

23 Guyette FX, Roth KR, LaCovey DC, Rittenberger JC. Feasibility of laryngeal  mask airway use by prehospital personnel in simulated pediatric respiratory arrest. Prehosp Emerg Care 2007; 11:245–249. This article explores the use of laryngeal mask airways for out-of hospital airway management in emergencies. 24 Mielke LL, Lanzinger MJ, Aschke C, et al. Plasma epinephrine levels after epinephrine administration using different tracheal administration techniques in adult CPR porcine model. Resuscitation 2001; 50:103–108. 25 Weiss M, Nicolai T. Cuffed pediatric tracheal tubes in emergency medicine. Notfall Rettungsmed 2006; 9:186–189. 26 Aufderheide TP, Sigurdsson G, Pirrallo RG, et al. Hyperventilation-induced hypotension during cardiopulmonary resuscitation. Circulation 2004; 109: 1960–1965. 27 Eberle B, Dick WF, Schneider T, et al. I. Checking the carotid pulse check: diagnostic accuracy of first responders in patients with and without a pulse. Resuscitation 1996; 33:107–116. 28 Owen CJ, Wyllie JP. Determination of heart rate in the baby at birth. Resuscitation 2004; 60:213–217. 29 Srikantan SK, Berg RA, Cox T, et al. Effect of one-rescuer compression/ ventilation ratios on cardiopulmonary resuscitation in infant, pediatric, and adult manikins. Pediatr Crit Care Med 2005; 6:293–297. 30 Hostler D, Guimond G, Callaway C. A comparison of CPR delivery with various compression-to-ventilation ratios during two-rescuer CPR. Resuscitation 2005; 65:325–328. 31 Whitelaw CC, Slywka B, Goldsmith LJ. Comparison of a two-finger versus two-thumb method for chest compressions by healthcare providers in an infant mechanical model. Resuscitation 2000; 43:213–216. 32 Langhelle A, Sunde K, Wik L, Steen PA. Airway pressure with chest compressions versus Heimlich manoeuvre in recently dead adults with complete airway obstruction. Resuscitation 2000; 44:105–108. 33 Thoresen M, Satas S, Puka-Sundvall M, et al. Posthypoxic hypothermia reduces cerebrocortical release of NO and excitotoxins. Neuroreport 1997; 8:3359–3362.

41 Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002; 346:549–556. 42 Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002; 346:557–563. 43 Eicher DJ, Wagner CL, Katikaneni LP, et al. Moderate hypothermia in neonatal encephalopathy: efficacy outcomes. Pediatr Neurol 2005; 32:11–17. 44 Battin MR, Penrice J, Gunn TR, et al. Treatment of term infants with head cooling and mild systemic hypothermia (35.0 degrees C and 34.5 degrees C) after perinatal asphyxia. Pediatrics 2003; 111:244–251. 45 Gunn AJ, Gluckman PD, Wyatt JS, et al. Selective head cooling after neonatal encephalopathy. Lancet 2005; 365:1619–1620. 46 Gluckman PD, Wyatt JS, Azzopardi D, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomized trial. Lancet 2005; 365:663–670. 47 Edwards AD, Azzopardi DV. Therapeutic hypothermia following perinatal asphyxia. Arch Dis Child Fetal Neonatal Ed 2006; 91:F127–F131. 48 Shankaran S, Laptook A, Ehrenkranz RA, et al. Whole body hypothermia for neonates with hypoxic ischemic encephalopathy. N Engl J Med 2005; 353:1574–1584. 49 Azzopardi D, Robertson NJ, Cowan FM, et al. Pilot study of treatment with whole body hypothermia for neonatal encephalopathy. Pediatrics 2000; 106:684–694. 50 Eicher DJ, Wagner CL, Katikaneni LP, et al. Moderate hypothermia in neonatal encephalopathy: safety outcomes. Pediatr Neurol 2005; 32:18–24. 51 Thoresen M, Whitelaw A. Cardiovascular changes during mild therapeutic hypothermia and rewarming in infants with hypoxic-ischemic encephalopathy. Pediatrics 2000; 106:92–99. 52 Gunn TR, Wilson NJ, Aftimos S, et al. Brain hypothermia and QT interval. Pediatrics 1999; 103:1079.

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