Part 7: Neonatal Resuscitation · Part 7: Neonatal Resuscitation 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment

Part 7: Neonatal Resuscitation2015 International Consensus on CardiopulmonaryResuscitation and Emergency Cardiovascular CareScience With Treatment Recommendations (Reprint)

Reprint: The American Heart Association requests that this document becited as follows: Perlman JM, Wyllie J, Kattwinkel J, Wyckoff MH, Aziz K,Guinsburg R, KimHS, Liley HG,Mildenhall L, SimonWM, Szyld E, TamuraM,Velaphi S; onbehalf of theNeonatal ResuscitationChapter Collaborators.Part 7: neonatal resuscitation: 2015 International Consensus on Car-diopulmonary Resuscitation and Emergency Cardiovascular Care Sci-ence With Treatment Recommendations. Circulation. 2015;132(suppl 1):S204–S241.

Reprinted with permission of the American Heart Association, Inc.,European Resuscitation Council, and International Liaison Committee onResuscitation. This article has been published in Circulation and Re-suscitation.

(Circulation. 2015;132[suppl 1]:S204–S241. DOI: 10.1161/CIR.0000000000000276.)

INTRODUCTION

Newborn Transition

The transition from intrauterine to extrauterine life that occurs at the timeof birth requires timely anatomic and physiologic adjustments to achievetheconversion fromplacental gasexchange topulmonary respiration. Thistransition isbroughtaboutby initiationofairbreathingandcessationof theplacental circulation. Air breathing initiates marked relaxation of pul-monary vascular resistance, with considerable increase in pulmonaryblood flow and increased return of now-well-oxygenated blood to the leftatrium and left ventricle, as well as increased left ventricular output.Removal of the low-resistance placental circuit will increase systemicvascular resistance and blood pressure and reduce right-to-left shuntingacrosstheductusarteriosus. Thesystemicorgansmustequallyandquicklyadjust to the dramatic increase in blood pressure and oxygen exposure.Similarly, intrauterine thermostability must be replaced by neonatalthermoregulation with its inherent increase in oxygen consumption.

Approximately 85% of babies born at term will initiate spontaneous res-pirations within 10 to 30 seconds of birth, an additional 10% will respondduring drying and stimulation, approximately 3% will initiate respirationsafter positive-pressure ventilation (PPV), 2% will be intubated to supportrespiratory function, and 0.1% will require chest compressions and/orepinephrine to achieve this transition.1–3 Although the vast majority ofnewborn infants do not require intervention to make these transitionalchanges, the large number of births worldwide means that many infantsrequire some assistance to achieve cardiorespiratory stability each year.

AUTHORS: Jeffrey M. Perlman, Co-Chair*; Jonathan Wyllie,Co-Chair*; John Kattwinkel; Myra H. Wyckoff; Khalid Aziz;Ruth Guinsburg; Han-Suk Kim; Helen G. Liley; LindsayMildenhall; Wendy M. Simon; Edgardo Szyld; MasanoriTamura; Sithembiso Velaphi; on behalf of the NeonatalResuscitation Chapter Collaborators

KEY WORDScardiopulmonary resuscitation n delivery room n newborns

www.pediatrics.org/cgi/doi/10.1542/peds.2015-3373D

doi:10.1542/peds.2015-3373D

*Co-chairs and equal first co-authors.

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2015 American Heart Association, Inc., EuropeanResuscitation Council, and International Liaison Committee onResuscitation.

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Newly born infants who are breathingor crying and have good tone immedi-ately after birth must be dried and keptwarmsoas toavoidhypothermia. Theseactions can be provided with the babylying on the mother’s chest and shouldnot require separation of mother andbaby. This does not preclude the needfor clinical assessment of the baby. Forthe approximately 5% of newly borninfants who do not initiate respiratoryeffort after stimulation by drying, andproviding warmth to avoid hypother-mia, 1 or more of the following actionsshould be undertaken: providing ef-fective ventilation with a face mask orendotracheal intubation, and adminis-tration of chest compressions with orwithout intravenous medications orvolume expansion for those with apersistent heart rate less than 60/minor asystole, despite strategies to achieveeffective ventilation (Figure 1).

The 2 vital signs that are used to identifytheneed foran interventionaswell as toassess the response to interventionsare heart rate and respirations. Pro-gression down the algorithm shouldproceed only after successful comple-tion of each step, themost critical beingeffective ventilation. A period of onlyapproximately 60 seconds after birth isallotted to complete each of the first 2steps, ie, determination of heart rateand institution of effective ventilation.Subsequent progression to the nextstep will depend on the heart rate andrespiratory response.

Evidence Evaluation

GRADE

The task force performed a detailedsystematic review based on the recom-mendations of the Institute ofMedicine ofthe National Academies4 and using themethodological approach proposed bythe Grading of Recommendations, As-sessment, Development and Evaluation(GRADE) Working Group.5 After identifi-cation and prioritization of the questions

to be addressed (using the PICO [pop-ulation, intervention, comparator, out-comes] format),6 with the assistance ofinformation specialists, a detailed searchfor relevant articles was performed ineach of 3 online databases (PubMed,Embase, and the Cochrane Library).

By using detailed inclusion and exclu-sion criteria, articleswere screened forfurther evaluation. The reviewers foreach question created a reconciled risk

of bias assessment for each of the in-cluded studies, using state-of-the-arttools: Cochrane for randomized con-trolled trials,7 Quality Assessment ofDiagnostic Accuracy Studies (QUADAS)-2for studies of diagnostic accuracy,8

and GRADE for observational studiesthat inform both therapy and progno-sis questions.9

GRADE is an emerging consensus pro-cess that rates quality of evidence and

Figure 1Neonatal Resuscitation Algorithm.

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strength of recommendations alongwith values and preferences. GRADEevidence profile tables10 were createdto facilitate an evaluation of the evi-dence in support of each of the criticaland important outcomes. The quality ofthe evidence (or confidence in the es-timate of the effect) was categorized ashigh (where one has high confidence inthe estimate of effect as reported ina synthesis of the literature), moderate(where one has moderate confidence,but there may be differences froma further elucidated truth), low (whereone has low confidence in the estimateof the effect that may be substantiallydifferent from the true effect), or verylow (where it is possible that the esti-mate of the effect is substantially dif-ferent from the true effect).11 Thesecategorizations were based on thestudy methodologies and the 5 coreGRADE domains of risk of bias, in-consistency, indirectness (ie, the pop-ulation studied was not the same asthat for which the guideline will beused), imprecision of effect estimates,and other considerations (includingpublication bias).12 Randomized stud-ies start as high quality but may bedowngraded for methodological qual-ity, whereas observational or cohortstudies start off as low quality and canbe further downgraded or upgradeddepending on methodical quality orpositive outcome effect.

Guideline users have to determine howmuch they can trust that a recommen-dation will produce more favorablerather thanunfavorable consequences.The strength of a recommendation re-flects a gradient in guidance, with aclearer expectation for adherence withstrong recommendations (identified bythe words we recommend) and lesserinsistence in weak recommendations(identified by the wordswe suggest). Inaddition, the direction of effect may bein favor of or against the recommen-dation. GRADE points to several factors

that may influence the strength ofa recommendation, including the risk-benefit balance, quality of evidence,patient values and preferences, and,finally, costs and resource utilization. Ifconfidence in these values and prefer-ences is high and variability is low, it ismore likely that the recommendationwill be strong (and vice versa). Rec-ommendations, whether strong orweak, have different implications forpatients, healthcare professionals, orhealthcare management.

Generation of Topics

Afterpublicationof the2010 InternationalConsensus on Cardiopulmonary Re-suscitation (CPR) and Emergency Car-diovascular Care ScienceWith TreatmentRecommendations (CoSTR),13–15 it wasapparent that several unclear and con-tentious delivery room resuscitationissues remained. In 2012, the NeonatalTask Force published an article titled“Neonatal Resuscitation: In Pursuit ofEvidence Gaps in Knowledge,”16 in whichthe major gaps in knowledge wereidentified. The following critical ran-domized studies were proposed withthe goal for completion before theILCOR 2015 International ConsensusConference on CPR and Emergency Car-diovascular Care ScienceWith TreatmentRecommendations:

� Prophylactic postdelivery endotra-cheal suctioning versus no suctioningin a depressed baby with meconium

� Comparison of different saturationpercentiles to use for targetingsupplementary oxygen delivery inuncompromised and compromisedpremature infants

� Comparison of prolonged versusconventional inspiratory times todetermine if the former is moreeffective in establishing functionalresidual capacity (FRC) and in-creasing the heart rate

� Studies to determine the optimumtechnique for maintaining the tem-

perature of very low birth weight(VLBW) infants from the time of de-livery through admission to inten-sive care

One small randomized study has ad-dressed the question of prophylacticendotracheal suctioning in the de-pressedbabywithmeconium17 (seeNRP865), and 1 randomized trial of sus-tained inflation (SI) has recently beenpublished18 (see NRP 804). Additionalstudies addressing these critical ques-tions are ongoing but were not availablefor the 2015 CoSTR review.

To achieve the goal of identifying a se-ries of relevant questions, the NeonatalTask Force group comprising 38 mem-bers and representing 13 countries metfor the first time in May 2012 in Wash-ington, DC. At that meeting, a series ofquestions were identified, researched,culled, and eventually refined into 26questions at subsequent meetings byusingtheGRADEapproach.Oneadditionalquestion, related to the accurate andtimely detectionof heart rate immediatelyafter birth, was identified in December2014 as a major gap in knowledge andwas introduced as a late-breaking PICOquestion. Themeetings since May 2012included 3 ILCOR group meetings (inVienna, October 2012; Melbourne, April2013; and Banff, April 2014) andneonatal-specific ILCOR meetings (inDenver, CO, May 2013; Washington, DC,December 2013; Vancouver, Canada,May 2014; and Washington, DC, De-cember 2014).

The literature was researched andconsensus was reached on the follow-ing issues:

� Optimal assessment of heart rate(NRP 898)

� Delayed cord clamping in preterminfants requiring resuscitation (NRP787)

� Umbilical cord milking (NRP 849)

� Temperature maintenance in thedelivery room (NRP 589)


https://volunteer.heart.org/apps/pico/Pages/PublicComment.aspx?q=865













� Maintaining infant temperatureduring delivery room resuscitation(NRP 599)

� Warming of hypothermic newborns(NRP 858)

� Babies born to mothers who arehypothermic or hyperthermic in la-bor (NRP 804)

� Maintaining infant temperatureduring delivery room resuscita-tion—intervention (NRP 793)

� Continuous positive airway pressure(CPAP) and intermittent positive-pressure ventilation (IPPV) (NRP 590)

� Sustained inflations (NRP 809)

� Outcomes for positive end-expiratorypressure (PEEP) versus no PEEP inthe delivery room (NRP 897)

� T-piece resuscitator and self-inflating bag (NRP 870)

� Intubation and tracheal suctioningin nonvigorous infants born throughmeconium-stained amniotic fluid(MSAF) versus no intubation for tra-cheal suctioning (NRP 865)

� Oxygen concentration for resuscitat-ing premature newborns (NRP 864)

� 2-Thumb versus 2-finger techniquesfor chest compression (NRP 605)

� Chest compression ratio (NRP 895)

� Oxygen delivery during CPR—neo-natal (NRP 738)

� Laryngeal mask airway (NRP 618)

� Newborn infants who receive PPVfor resuscitation, and use of a de-vice to assess respiratory function(NRP 806)

� Use of feedback CPR devices forneonatal cardiac arrest (NRP 862)

� Limited resource–induced hypo-thermia (NRP 734)

� Delivery room assessment for lessthan 25 weeks and prognosticscore (NRP 805)

� Apgar score of 0 for 10 minutes orgreater (NRP 896)

� Predicting death or disability ofnewborns of greater than 34weeks based on Apgar and/or ab-sence of breathing (NRP 860)

� Resuscitation training frequency(NRP 859)

� Neonatal resuscitation instructors(NRP 867)

NEONATAL ALGORITHM

There was considerable debate withregard to modifying the algorithm. Thefirst debate related to the necessity ofa timeline. Many thought that a 30-sec-ond time rulewas unreasonable andnotevidenced based. On the other hand,because this is a global document,others advocated strongly that a re-minder to assess and intervene if nec-essary, within 60 seconds after birth,should be retained to avoid criticaldelays in initiationof resuscitation. Thus,more than95%ofnewlyborn infantswillstart breathing spontaneously or in re-sponse to stimulation within approxi-mately 30 seconds.1 If apnea persistsPPV should be initiated within 60 sec-onds. As a compromise, the 30-secondtime point has been removed. Given theimportance of hypothermia as a pre-dictor of mortality and evidence frommultiple studies that moderate hypo-thermia (temperature less than 36°C)can be avoided with simple interventionstrategies, the new algorithm containsa running line reminding providers tomaintain thermoregulation throughoutthe immediate newborn period.

INITIAL ASSESSMENT ANDINTERVENTION

ECG/EKG in Comparison to Oximetryor Auscultation for the Detection ofHeart Rate (NRP 898)

In babies requiring resuscitation (P),doeselectrocardiography(ECG/EKG) (I),compared with oximetry or ausculta-tion (C), measure heart rate faster andmore accurately (O)?

Introduction

Neonatal resuscitation success hasclassically been determined by detect-ing an increase in heart rate throughauscultation. Heart rate also deter-mines the need for changing inter-ventions and escalating care. However,recent evidence demonstrates thatauscultation of heart rate is inaccurateand pulse oximetry takes severalminutes to achieve a signal and alsomay be inaccurate during the earlyminutes after birth. This PICO questionis intended to review the evidence re-garding how best to determine heartrate after birth.

Consensus on Science

For the important outcomesof fastandaccurate measurement of heartrate in babies requiring resuscitation,we have identified

� Very-low-quality evidence from 5nonrandomized studies enrolling213 patients showing a benefit ofECG compared with oximetry19–23

� Very-low-quality evidence from 1nonrandomized study enrolling 26patients showing a benefit of ECGcompared with auscultation24

The available evidence is from non-randomized studies, downgraded forindirectness and imprecision.

Treatment Recommendation

In babies requiring resuscitation, wesuggest the ECG can be used to providea rapid and accurate estimation ofheart rate (weak recommendation,very-low-quality evidence).

Values, Preferences, and Task ForceInsights

There wasmuch discussion and heateddebate about the use of ECG to de-termine heart rate. Although the datasuggest that the ECG provides a moreaccurate heart rate in the first 3minutes, therewerenoavailabledata todeterminehowoutcomeswouldchange

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by acting (or not acting) on the in-formation. Important issues wereraised about inappropriate inter-ventions being implemented based ona falsely low heart rate by pulse oxi-metry or auscultation that might beavoided if the heart rate could be de-terminedbyECG. Itwaspointedout thatpulse oximetry is still very importantfor the measurement of saturationvalues to define supplementary oxygenneeds. Introducing ECG leads in thedelivery room will take time, as willacquiring methods to rapidly applyelectrodes. In view of these findings offalse-positive readings by conven-tional means, we have no data onwhento advise appropriate actions forbradycardia detected by the conven-tional measures such as pulse oxi-metry or auscultation. Some transientbradycardia may be normal and bereflective of timing of cord clamping.More studies are needed.

Knowledge Gaps

� Studies delineating differences ininterventions and/or patient out-comes based on ECG versus pulseoximetry measurements

� Studies of heart rate in VLBW infantsrequiring resuscitation and in rela-tionship to timing of cord clamping

� Improved technology for rapid ap-plication of ECG

Delayed Cord Clamping in PretermInfants Requiring Resuscitation(Intervention) (NRP 787)

In preterm infants, including those whoreceived resuscitation (P), doesdelayed cord clamping (greater than 30seconds) (I), comparedwith immediatecord clamping (C), improve survival,long-term developmental outcome,cardiovascular stability, occurrence ofintraventricular hemorrhage (IVH),necrotizing enterocolitis, temperatureon admission to a newborn area, andhyperbilirubinemia (O)?

Introduction

In the past 50 years, the umbilical cordsof babies born preterm have generallybeen cut soon after birth, so that thenewborns can be transferred immedi-ately to the neonatal team. However,there is recent evidence that a delay ofclampingby 30 to 60 secondsafter birthresults in a smoother transition, par-ticularly if the baby begins breathingbefore the cord is cut. In both animaland human models, the delay is asso-ciated with increased placental trans-fusion, increased cardiac output, andhigher and more stable neonatal bloodpressure. There is controversy abouthow long it is appropriate to delayclamping if the baby is perceived torequire resuscitation.


For the critical outcome of infantdeath, we identified very-low-quality(downgraded for imprecision and veryhigh risk of bias) evidence from 11randomized clinical trials enrolling591 patients showing no benefit todelayed cord clamping (odds ratio[OR], 0.6; 95% confidence interval [CI],0.26–1.36).25–35

For the critical outcome of severe IVH,we identified very-low-quality evidence(downgraded for imprecision and veryhigh risk of bias) from 5 randomizedclinical trials enrolling 265 patientsshowing no benefit to delayed cordclamping (OR, 0.85; 95% CI, 0.20–3.69).26,27,31,32

For the critical outcome of periven-tricular hemorrhage (PVH)/IVH, weidentified very-low-quality evidence(downgraded for imprecision and veryhigh risk of bias) from 9 randomizedclinical trials enrolling 499 patientsshowing benefit of delayed cordclamping (OR, 0.49; 95% CI, 0.29–0.82).26,27,29–35

For the critical outcome of neuro-development, we did not identify anyevidence.

For the critical outcome of cardio-vascular stability as assessed bymean blood pressure at birth, weidentified very-low-quality evidence(downgraded for imprecision and veryhigh risk of bias) from 2 randomizedclinical trials enrolling 97 patientsshowing higher blood pressure asso-ciated with delayed cord clamping(mean difference [MD], 3.52; 95% CI,0.6–6.45).29,31

For the critical outcome of cardio-vascular stability as assessed bymean blood pressure at 4 hours afterbirth, we identified very-low-qualityevidence (downgraded for impreci-sion and very high risk of bias) from 3randomized clinical trials enrolling 143patients showing increased meanblood pressure at 4 hours of age afterdelayed cord clamping (MD, 2.49; 95%CI, 0.74–4.24).25,31,32

For the critical outcome of cardio-vascular stability as assessed byblood volume, we identified very-low-quality evidence (downgraded for im-precision and very high risk of bias)from 2 randomized clinical trials en-rolling 81 patients showing benefit ofdelayed cord clamping (MD, 8.25; 95%CI, 4.39–12.11).35,36

For the critical outcome of tempera-ture, on admission we identified very-low-quality evidence (downgraded forimprecision and very high risk of bias)from 4 randomized clinical trials en-rolling 208 patients showing no statis-tically significant benefit from delayedcord clamping (MD, 0.1; 95% CI, 20.04to 0.24).29,31,32,34

For the important outcome of need fortransfusion, we identified very-low-quality evidence from 7 randomizedclinical trials enrolling 398 patientsshowing less need for transfusion afterdelayed cord clamping (OR, 0.44; 95%CI, 0.26–0.75).28–30,32,34–36

For the important outcome of necro-tizing enterocolitis, we identified



very-low-quality evidence (downgradedfor imprecision and very high risk ofbias) from 5 randomized clinical trialsenrolling 241 patients showing lowerincidence of necrotizing enterocolitis(OR, 0.3; 95% CI, 0.19–0.8).29,31–34

For the important outcome of hyper-bilirubinemia and peak bilirubin con-centrations (mmol/L), we identifiedmoderate-quality evidence from 6 ran-domized clinical trials enrolling 280patients showing higher peak bilirubinvalue in those neonates with delayedcord clamping (MD, 16.15; 95% CI, 6.13–26.17).29–33,35

For the important outcome of treatedhyperbilirubinemia (need for photo-therapy), we identified low-quality evi-dence from 1 randomized clinical trialenrolling 143 patients showing no sta-tistically significant difference (relativerisk [RR], 1.29; 95% CI, 1.00–1.67).35


We suggest delayed umbilical cordclamping for preterm infants not re-quiring immediate resuscitation afterbirth (weak recommendation, very-low-quality evidence).

There is insufficient evidence to rec-ommend an approach to cord clampingfor preterm infants who do receive re-suscitation immediately after birth, be-causemanybabieswhowereathighriskofrequiringresuscitationwereexcludedfrom or withdrawn from the studies.


Overall, the quality of evidence for thequestion was very low. Despite drawingevidence from randomized controlledtrials, the small sample size in mosttrials and the associated imprecisionlimited the quality of evidence for alloutcomes of interest. Although 2 largerobservational trials were considered,the quality and size of effect were notsufficient to influence the conclusions.The quality of evidence for necrotizing

enterocolitis and hyperbilirubinemiawas limited by inconsistent definitionsof the outcome, and inconsistentthresholds for treatment with photo-therapy across studies.

� Balance of consequences favorsdelayed cord clamping, as desir-able consequences probably out-weigh undesirable consequencesin most settings. The results ofrandomized controlled trials andnonrandomized observational stud-ies with comparison groups weregenerally consistent. However, smalland sick infants who received im-mediate resuscitation were gener-ally excluded from the availablerandomized controlled trials, sodata are very limited for this groupat highest risk for physiologic insta-bility, complications of prematurity,and mortality who may also realizehighest benefit or harm from theintervention.

� Preferences (parents’) favordelayed clamping, which has re-ceived strong popular supportthrough social media and Inter-net sites. The advantages of delayedcord clamping assume heightenedimportance in resource-limited set-tings where specialty care for pre-term neonates may be limited.Improving initial cardiovascular sta-bility with maintenance of tempera-ture and lower risk of morbiditiessuch as necrotizing enterocolitisand severe intracranial hemor-rhage may offer significant survivaladvantages, even where neonatalintensive care is not available. Inareas where maternal anemia isprevalent, iron supplementationis limited, and a safe blood supplyis often unavailable, the reductionin need for transfusion and im-proved blood volume at birth mayhave increased significance.

Amajordebate surrounded the issueastowhether thequalityof thestudieswas

low or very low. Overall, the groupthought that downgrading the evidenceas suggestedby theGRADE toolwasnotreasonable, given that this was one ofthe areas with the most randomizedtrial data. However, eventually basedon theGRADE criteria, it wasnecessaryto classify most of the outcomes asvery-low-quality evidence. It was notedthat the existing studies enrolled veryfew extremely premature infants andvery few who received resuscitation.The groupwas unanimous in stressingthe need for additional research,which parallels a Cochrane reviewreflecting similar sentiments of a needfor more high-quality evidence. Somemembers questioned how to reconcilewith obstetric guidelines, which hasan out clause for babies requiringresuscitation.37

Knowledge Gaps

� Results of ongoing large random-ized controlled trials

� Comparison of delayed versusimmediate cord clamping amongpreterm infants who receive resus-citation with PPV

� Comparison of delayed cordclamping with cord milking

� Outcome data of high importance,such as long-term neurodevelop-ment

� Need for resuscitative interventionat delivery

� Hyperbilirubinemia among high-risk populations

Umbilical Cord Milking—Intervention (NRP 849)

In very preterm infants (28 weeks orless) (P), does umbilical cord milking(I), in comparison with immediate um-bilical cord clamping (C), affect death,neurodevelopmental outcome at 2 to 3years, cardiovascular stability, ie, needfor pressors, need for fluid bolus, initialmean blood pressure, IVH (any grade,

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severegrade),temperatureonadmission,hematologic indices, (initial hemoglobin,need for transfusion), hyperbilirubinemia,need for phototherapy, or need for ex-change transfusion (O)?

Introduction

There is someevidence that “milking”ofthe umbilical cord from the placentalside toward the newborn may havea similar effect to delayed cordclamping (ie, increased placentaltransfusion, improved cardiac output,and increased neonatal blood pres-sure). If correct, this would offera more rapid alternative to delayedclamping of the cord.


For the critical outcome of death, wefound low-quality evidence (down-graded for very serious imprecision)from 3 randomized clinical trials38–40

showing that there is no difference indeath (OR, 0.76; 95% CI, 0.25–2.29).

For the critical outcome of cardio-vascular stability, we found low-quality evidence (downgraded forimprecision) from 2 randomized stud-ies38,39 showing that the initial meanblood pressure was 5.43 mm Hg higher(range, 1.98–8.87 mm Hg) in the groupreceiving umbilical cord milking.

For the critical outcome of IVH, wefound low-quality evidence (down-graded for very serious imprecision)from 2 randomized clinical trials38,40

showing a reduction of IVH (all grades:OR, 0.37; 95% CI, 0.18–0.77) but no dif-ference (from 1 randomized clinicaltrial38 in severe IVH; OR, 0.44; 95% CI,0.07–2.76) (low-quality evidence,downgraded for very serious impreci-sion) when umbilical cord milking wasperformed.

For the critical outcome of neurologicoutcome at 2 to 3 years, we did notidentify any evidence to address this.

For the important outcome of hema-tologic indices, we found low-quality

evidence (downgraded for impreci-sion) from 2 randomized clinical tri-als38,39 showing that cord milkingincreased the initial hemoglobin level(MD, 2.27 g/dL; 95% CI, 1.57–2.98 g/dL)and low-quality evidence (downgradedfor imprecision) from 3 randomizedclinical trials38–40 showing that cordmilking decreased transfusion (OR, 0.2;95% CI, 0.09–0.44).

For the important outcome of tem-perature, we found low-quality evi-dence (downgraded for very seriousimprecision) from 1 randomized clini-cal trial39 showing that the tempera-ture of the milking group was notdifferent on admission.

For the important outcome of bilirubinindices, we found low-quality evidence(downgraded for very serious impre-cision) showing that the maximumbilirubin measurement (3 randomizedclinical trials38–40) and use of photo-therapy (1 study40) was not differentbetween groups.


We suggest against the routine use ofcordmilking for infants born at 28weeksof gestation or less, because there isinsufficient published human evidence ofbenefit. Cord milking may be consideredon an individual basis or in a researchsetting, as it may improve initial meanblood pressure and hematologic indicesand reduce intracranial hemorrhage.There is no evidence for improvement inlong-term outcomes (weak recommen-dation, low-quality evidence).

All studies included in this evidencereview milked 20 cm of umbilical cordtoward the umbilicus 3 times while theinfant was held at the level of theintroitus or below the level of the pla-centa before cord clamping.


In making this recommendation, weplace a higher value on the unknown

safety profile and less value on thesimplicity/economyof this intervention.

Much of the deliberations focused onthe wording of the treatment recom-mendation. The first recommendationproposed was, “We suggest that cordmilking, as opposed to immediatecord clamping, be performed at de-livery for VLBW infants.” A secondrecommendation was, “We suggestthat cord milking, as opposed to im-mediate cord clamping, may be per-formed at delivery for VLBW butshould not be regarded as a standardof care.” A third recommendationwas, “We suggest that cord milking,as opposed to immediate cordclamping, may be performed at de-livery for VLBW to improve initial meanblood pressure, hematologic indices,and IVH (Grades 1 and 2).” However,concerns were raised related to theabsence of evidence pertinent to long-term outcomes and, in particular,neurologic outcome. Moreover, therewas serious imprecision in the data.These factors led to the final treatmentrecommendation.

Knowledge Gaps

� Evidence regarding neurodevelop-mental outcomes for cord milkingcompared with immediate cordclamping is necessary.

� Comparison of delayed cord clamp-ing with cord milking

� Multiple studies of cord milking inthis population are under way atthis time, and additional data willbe available in 2020.

TEMPERATURE

It has been known for more thana century that preterm babies whobecome hypothermic after birth havea higher mortality than those who re-main normothermic.41 The associationbetween hypothermia and neonatalmortality and morbidity, including


respiratory distress syndrome, meta-bolic derangements, IVH, and late-onset sepsis, has long been recog-nized, with premature infants beingparticularly vulnerable (see below).Specifically, moderate hypothermia(temperature less than 36°C) at birthhas been recognized as an in-dependent risk factor for death inpremature infants.42,43

These relationships reflect the fact thatthe premature infant is at very high riskof net heat loss because of a largesurface area–to–volume ratio and in-creased evaporative fluid losses fromthe skin. Strategies introduced to min-imize heat loss include use of occlusivewrapping, exothermic warming mat-tress, warmed humidified resuscitationgases, polyethylene caps, and increasingdelivery room temperature, and havemet with varying success. A by-productof these interventions to prevent hypo-thermia is more-frequent hyperthermia(temperature greater than 37.5°C). Hy-perthermia (temperature greater than37.5°C) also increases the risk for neo-natal mortality and morbidity in bothterm and preterm infants. This sectionwill review the importance of maintain-ing temperature in a goal range, inter-ventions to minimize heat loss atdelivery, how quickly a low temperatureshould be raised into a normal range, theimpact of maternal hyperthermia andhypothermia on the newborn, and strat-egies to avoid hypothermia in theresource-limited setting.

Temperature Maintenance in theDelivery Room—Prognosis (NRP589)

In nonasphyxiated babies at birth (P),does maintenance of normothermia(core temperature 36.5°C or greaterand 37.5°C or less) from delivery toadmission (I), compared with hypo-thermia (less than 36°C) or hyper-thermia (greater than 37.5°C) (C),change survival to hospital discharge,

respiratory distress, survival to ad-mission, hypoglycemia, intracranialhemorrhage, or infection rate (O)?


For the critical outcome of mortality,there is evidence from 36 observa-tional studies of increased risk ofmortality associated with hypothermiaat admission42–77 (low-quality evidencebut upgraded to moderate-quality evi-dence due to effect size, dose-effectrelationship, and single direction ofevidence). There is evidence of a doseeffect on mortality, suggesting an in-creased risk of at least 28% for each 1°below 36.5°C body temperature at ad-mission42,43 and dose-dependent effectsize.42,43,48,66 One small randomizedclinical trial78 (very-low-quality evi-dence, downgraded for indirectnessand serious imprecision) showed a re-duction in adverse events, includingdeath, intracranial hemorrhage, nec-rotizing enterocolitis, and oxygen de-pendence with improved temperaturemanagement, but 3 randomized con-trolled trials79–81 (low-quality evidence,downgraded for indirectness and im-precision) did not show any significantimprovement in mortality with signifi-cantly improved temperature control.Four observational studies60,61,63,82

(very-low-quality evidence, down-graded for indirectness and impreci-sion) did not find any improvement inmortality with improved admissiontemperatures, but they were not suffi-ciently powered for this outcome.

For the critical outcome of IVH, 8 ob-servational studies (very-low-qualityevidence, downgraded for risk of biasand indirectness) show hypothermia(temperature less than 36°C) in pre-term infants is associated with an in-creased likelihood of developingIVH.48,55,66,83–87 Eight observationalstudies (low-quality, downgraded forindirectness) found no association be-tween hypothermia and IVH.43,60,61,88–92

For the important outcome of re-spiratory issues, there is evidence from9 observational studies44,48,50,67,83,93–96

(low-quality evidence) showing an asso-ciation between hypothermia and re-spiratory disease. One large randomizedcontrolled trial79 (low-quality evidence,downgraded for imprecision and risk ofbias) found a reduction in pulmonaryhemorrhage associated with improvedadmission temperature (OR, 0.57; 95% CI,0.35–0.94). Eight observational studies(very-low-quality evidence) have shownan improvement in respiratory out-comes after improved admission tem-perature maintenance.44,49,51,63,72,84,93,95

Two of these have shown a decrease inrespiratory support with improvedtemperature maintenance.93,96 Twoobservational studies (very-low-qualityevidence, downgraded for indirectnessand imprecision) did not show any as-sociation.43,60

For the serious outcome of hypogly-cemia, there were seven observationalstudies (very-low-quality, downgradedfor risk of bias and indirectness)showing a significant association be-tween hypothermia (less than 36°C)and hypoglycemia.44,67,70,97–100 Two ofthese studies, using historical controls,showed improved glycemic controlwith improved normothermia.44,99

For the serious outcome of late sepsis,2 observational studies (very-low-quality evidence, downgraded for riskof bias and indirectness) indicated anassociation between hypothermia onadmission and late sepsis.43,101 Oneobservational study (low-quality, down-graded for risk of bias and indirectness)found no association after multivariateanalysis.66

For the serious outcome of survival toadmission, there is no published evi-dence addressing any effect of deliveryroom hypothermia upon survival toadmission.

For the serious outcome of admissionhyperthermia, there is no published

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evidence about newborn hyperthermiaat admission.

Treatment Recommendations

Admission temperature of newly bornnonasphyxiated infants is a strongpredictor of mortality and morbidity atall gestations. It should be recorded asa predictor of outcomes as well asa quality indicator (strong recommen-dation, moderate-quality evidence).

We recommend that the temperature ofnewly born nonasphyxiated infants bemaintained between 36.5°C and 37.5°Cafter birth through admission andstabilization (strong recommendation,very-low-quality evidence).


In making these statements, we placeahigher valueon thestrongassociationof inadvertent hypothermia withmortality, the apparent dose effect,the single direction of the evidence,the universal applicability, and theevidence for intervention improvingrespiratory outcomes over the lack ofmodern evidence for interventionchanging mortality.

The group thought that this questionshould change to a prognostic one. Arecurring question is whether some ofthe babies stay cold because of in-trinsic factors. However, there aredata that hypothermia upon admis-sion impacts mortality through atleast the first 6 months. It was sug-gested that a low temperature mayalso be related to the quality of careand environment. Most studies re-viewed used an axillary temperaturebut some older studies utilized a rectaltemperature. The relative benefits ofone over the other were not assessedin this PICO. The task force felt that anaxillary temperature should be used inthe delivery room but that on admis-sion it should be left to individual re-gional practice.

Knowledge Gaps

� Further studies are required tofind if improved admission temper-ature improves mortality andother outcomes.

Maintaining Infant TemperatureDuring Delivery RoomResuscitation—Intervention (NRP599)

Among preterm neonates who are un-der radiant warmers in the hospitaldelivery room (P), does increased roomtemperature, thermal mattress, or an-other intervention (I), compared withplastic wraps alone (C), reduce hypo-thermia (less than 36°C) on admissionto neonatal intensive care unit (NICU)(O)?

Introduction

A variety of strategies have been sug-gested to maintain a preterm infant’stemperature; it is unknown which ofthese strategies is/are most effective.This PICO question was intended toidentify the strategies and techniquesthat might be most effective.


Thermal Mattress Plus Plastic WrapPlus Radiant Warmer (I) Versus PlasticWrap Plus Radiant Warmer

For the critical outcome of hypo-thermia (temperature less than36.0°C) at NICU admission, we identi-fied low-quality evidence (down-graded for serious risk of bias) from 1randomized controlled trial102 enroll-ing 72 preterm infants of less than 32weeks of gestation showing no benefitto addition of a thermal mattress tothe use of plastic wrap and radiantwarmer (RR, 1.89; 95% CI, 0.18–19.95).Four observational studies (low-qualityevidence, downgraded for serious riskof bias)82,103–105 including 612 patientsof less than 32 weeks of gestationshowed benefit to the addition of thethermal mattress (OR, 0.27; 95% CI,0.18–0.42).

For the important outcome of hy-perthermia (temperature greaterthan 38.0°C) at admission, we haveidentified low-quality evidence (down-graded for serious risk of bias) fromthe same randomized controlled tri-al102 and4 observational studies82,103,105,106

including 426 patients showing no harmfrom the thermal mattress (RR, 3.78;95% CI, 0.86–16.60 and OR, 6.53; 95% CI,0.80–53.30).

Environmental Temperature 26°C orGreater Plus Plastic Wrap Plus RadiantWarmer (I) Versus Plastic Wrap PlusRadiant Warmer (C)

For the critical outcome of hypothermia(temperature less than 36.0°C) at NICUadmission, we identified no studiesaddressing this intervention alone.

For the important outcome of hy-perthermia (temperature greaterthan 38.0°C) at admission, we identifiedlow-quality evidence (downgraded forserious risk of bias) from 1 observa-tional study107 including 40 patients ofless than 29 weeks of gestation show-ing no harm from increasing the envi-ronmental temperature 26°C or greater(OR, 8.45; 95% CI, 0.37–182.58).

Heated and Humidified Gases Plus Plas-tic Wrap Plus Radiant Warmer (I) VersusPlastic Wrap Plus Radiant Warmer (C)

For the critical outcome of hypo-thermia (temperature less than 36.0°C)at NICU admission, we identified very-low-quality evidence (downgraded forserious risk of bias) from 1 randomizedcontrolled trial78 enrolling 203 patientsof less than 32 weeks of gestationshowing no benefit (RR, 0.64; 95% CI,0.31–1.35), and 1 observational study(low-quality evidence)108 including 112patients of less than 33 weeks of ges-tation showing benefit to the use ofheated and humidified gases and to theuse of plastic wrap and the radiantwarmer (OR, 0.20; 95% CI, 0.08–0.47).

For the important outcome of hy-perthermia (temperature greater than




38.0°C) at admission, we identified low-quality evidence (downgraded for seri-ous risk of bias) from the same obser-vational study108 showing no harm (OR,not estimable).

Total Body and Head Plastic Wrap PlusRadiant Warmer (I) Versus Body PlasticWrap Plus Radiant Warmer (C)

For the critical outcome of hypother-mia (temperature less than 36.0°C) atNICU admission, we identified very-low-quality evidence (downgraded for seri-ous risk of bias) from 1 randomizedcontrolled trial109 enrolling 100 patientsof less than 29 weeks of gestationshowing no benefit to the addition ofwrapping (RR, 0.60; 95% CI, 0.24–1.53).

For the important outcome of hy-perthermia (temperature greater than38.0°C) at admission, we identifiedlow-quality evidence (downgraded forserious risk of bias) from the samerandomized controlled trial109 showingno harm (RR, 0.33; 95% CI, 0.01–7.99).

Combination of Interventions (Envi-ronmental Temperature 23°C to 25°CPlus Plastic Wrap Without Drying PlusCap Plus Thermal Mattress Plus Radi-ant Warmer) Versus Plastic Wrap PlusRadiant Warmer (C)

For the critical outcome of hypo-thermia (temperature less than36.0°C) at admission, we identified very-low-quality evidence (downgraded forserious risk of bias) from 4 observa-tional studies93,95,96,110 enrolling 9334patients of less than 35 weeks of ges-tation showing benefit from usinga combination of interventions (ie, en-vironmental temperature 23°C to 25°Cplus plastic wrap without drying pluscap plus thermal mattress plus radiantwarmer; OR, 0.40; 95% CI, 0.35–0.46).

For the important outcome of hy-perthermia (temperature greater than38.0°C) at admission, we have identifiedlow-quality evidence (downgraded forserious risk of bias) from 3 observa-tional studies93,95,110 enrolling 8985

patients showing no harm to the com-bination of interventions (OR, 1.12; 95%CI, 0.82–1.52).


Among newly born preterm infants ofless than 32 weeks of gestation underradiant warmers in the hospital de-livery room, we suggest using a com-bination of interventions, which mayinclude environmental temperature23°C to 25°C, warm blankets, plasticwrapping without drying, cap, andthermal mattress to reduce hypother-mia (temperature less than 36.0°C) onadmission to NICU (weak recommen-dation, very-low-quality evidence).

We suggest that hyperthermia (greaterthan 38.0°C) be avoided due to the po-tential associated risks (weak recom-mendation, very-low-quality evidence).


We place value on the large numbersenrolled in the observational studiesand consistent direction of effect.

Because many of the studies usedmultiple strategies, it was not possibleto identify the different specific inter-ventions that are effective in main-taining temperature. There wasconcern whether the recommendationshould be so strong when the CIs forhyperthermia (0.80–53.30) comprising3 studies are so wide, raising the po-tential chance for harm. A strong rec-ommendation was made because ofthe large numbers in the studies andthe consistent direction of effect. Therewas concern about 1 randomizedthermal mattress trial, which wasstopped for safety issues because ofhyperthermia. However, this is the onlystudy that has demonstrated an ad-verse effect with small numbers, sug-gesting some unclear negative(possible environmental) effect. In thetreatment recommendation, it wassuggested to add the words may in-clude after the word combination.

Knowledge Gaps

� Although a combination of inter-ventions (increasing environmen-tal temperature, warm blankets,thermal mattress, and cap) linkedto quality improvement initiativesare effective in reducing hypother-mia (less than 36°C) on NICU ad-mission among newly born preterminfants of less than 32 weeks ofgestation who are under radiantwarmers and plastic wrap, the con-tribution of each intervention (in-creasing environmental temperature,thermal mattress, heated and hu-midified gases, and cap) remainsto be established.

Warming of Hypothermic Newborns—Intervention (NRP 858)

In newborns who are hypothermic(temperature less than 36.0°C) on ad-mission (P), does rapid rewarming(I), compared with slow rewarming(C), change mortality rate, short andlong-term neurologic outcome, hem-orrhage, episodes of apnea and hy-poglycemia, or need for respiratorysupport (O)?

Introduction

Neonates are at high risk for becominghypothermic during resuscitation.Some early teaching for rewarmingtheseneonateshassuggested that slowrewarming is preferable over faster soas toavoidcomplicationssuchasapneaand arrhythmias. This PICO question isintended to review the recent evidenceon this issue.


We identified2 randomized trials111,112

and 2 observational studies113,114

comparing rapid (greater than 0.5°C/hour) versus slow (less than 0.5°C/hour) rewarming strategies forhypothermic newborns (less than36.0°C) on admission. All studieswere dated (the most recent study

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was published 28 years ago) andconducted in different settings (2 inlow-resource countries and 2 inhigh-resource countries); enrolledpatients had different baseline char-acteristics (postnatal age, gestationalage, proportion of outborn/inborn, de-gree of hypothermia). The quality of thestudies was very poor in terms of num-ber of enrolled patients, inclusion cri-teria, randomization methods, studydesign, and outcome measures.

For the critical outcome of mortality,we identified low-quality evidence(downgraded for serious risk of bias)from 1 randomized clinical trial112 in-cluding 30 patients showing no benefit(RR, 0.88; 95% CI, 0.36–2.10) and 2 ob-servational studies113,114 including 99patients showing benefit in favor ofa rapid rewarming strategy (OR, 0.23;95% CI, 0.06–0.83).

For the critical outcome of convulsions/seizures, we identified very-low-qualityevidence (downgraded for serious riskof bias) from 1 randomized clinical tri-al112 including 30 patients showing nobenefit to rapid versus slow rewarming(RR, 0.88; 95% CI, 0.14–5.42).

For thecriticaloutcomeofhemorrhage/pulmonary hemorrhage, we identifiedvery-low-quality evidence (downgradedfor serious risk of bias) from 1 ran-domized clinical trial112 including 30patients and 1 observational study113

including 38 patients showing no bene-fit to rapid versus slow rewarming (RR,1.31; 95% CI, 0.26–6.76 and OR, 0.16; 95%CI, 0.02–1.50, respectively).

For the important outcome of need forrespiratory support, we identifiedvery-low-quality evidence (downgradedfor serious risk of bias) from 1 obser-vational study114 including 56 patientsshowing benefit in a slower over a rapidrewarming strategy (OR, 7.50; 95% CI,2.14–26.24).

For the important outcomeofepisodesof hypoglycemia, we identified very-

low-quality evidence (downgraded forserious risk of bias and very seriousimprecision) from 1 randomized con-trolled trial111 including 36 patientsand 1 observational study114 including56 patients showing no benefit to rapidversus slow rewarming (RR, 0.11; 95%CI, 0.01–1.81 and OR, 0.21; 95% CI, 0.01–4.06, respectively).

For the important outcomeofepisodesof apnea, we identified very-low-qualityevidence (downgraded for serious riskof bias and very serious imprecision)from 2 randomized clinical trials111,112

including 66 patients showing no bene-fit to rapid versus slow rewarming (RR,0.44; 95% CI, 0.04–4.32).


The confidence in effect estimates is solow that a recommendation for eitherrapid (0.5°C/hour or greater) or slowrewarming (0.5°C/hour or less) of un-intentionally hypothermic newborns(T° less than 36°C) at hospital admis-sion would be speculative.


It was considered important to distin-guish the warming of infants wherehypothermia is iatrogenic after birth,which in general is of a short duration,from hypothermia that is therapeuticandhasbeen intentionally inducedover72 hours. The latter rewarming isgenerally recommended to be slow.

Knowledge Gaps

� Attempts should be made to studya more homogenous patient popu-lation with specific inclusion crite-ria stratified by gestational andpostnatal age, severity of hypother-mia on admission, and commonoutcome measures.

� Addressing these factors with at-tention to power of the study byusing a multicenter study designwill generate useful data on which

to base decisions on the re-warming strategy for hypothermicnewborns.

Babies Born to Mothers Who AreHypothermic or Hyperthermic inLabor—Prognosis (NRP 804)

In newborn babies (P), does maternalhypothermia or hyperthermia in labor(I), versus normal maternal tempera-ture (C), result in adverse neonataleffects (O)?Outcomes includemortality,neonatal seizures, and adverse neuro-logic states.

Introduction

There is substantial literature fromobservational studies indicating anassociation between maternal hyper-thermia and neonatal mortality andmorbidity (see NRP 589). However, themechanisms linking these associationsremain unclear. In addition, the impactof maternal hypothermia on neonataloutcome remains unclear. This PICOquestion attempts to address thisissue.


Maternal Hyperthermia

For the critical outcome of mortality,we identified low-quality evidence from2 nonrandomized clinical trials(downgraded for risk of bias) showingan increased risk with maternal hy-perthermia.115,116

For the important outcome of neo-natal seizures, we identified low-quality evidence from 7 nonrandomizedclinical trials (downgraded for risk ofbias) showing an increased risk withmaternal hyperthermia.115–121

For the important outcome of ad-verse neurologic states (enceph-alopathy), we identified low-qualityevidence from 4 nonrandomized clinicaltrials (downgraded for risk of bias)showing an increased risk with mater-nal hyperthermia.122–125










Maternal Hypothermia

For the critical outcomeofmortalityand the important outcomes of seiz-ures or adverse neurologic states(encephalopathy), we identified very-low-quality evidence from 5 random-ized clinical trials (downgraded forvery serious indirectness) that showedno significant risk of these outcomeswith maternal hypothermia.126–130

However, the above studies did notspecifically examine these outcomes.

There are no studies of neonataloutcomes after interventions to keepmothers normothermic.


Although maternal hyperthermia isassociated with adverse neonatal out-comes, there is insufficient evidence tomake a recommendation regarding themanagementofmaternalhyperthermia.

There is insufficient evidence to makea treatment recommendation aboutmaternal hypothermia.


There was discussion as to whetherthis is a prognostic versus a thera-peutic question. The worksheet authorsused observational studies, becausethe randomized clinical trials didnot focus on the outcomes targeted.There was discussion as to whetherit was possible to separate hypo-thermia from the cause of hypother-mia.

Knowledge Gaps

� There are no randomized con-trolled trials of neonatal outcomesafter interventions to keep moth-ers normothermic.

� Do interventions to achieve normo-thermia in mothers who are hyper-thermic decrease risk of adverseoutcomes for newborns? (Lack ofrandomized clinical trials)

� Do interventions to achieve normo-thermia in mothers who are hypo-thermic decrease risk of adverseoutcomes for newborns? (Lack ofcritical/important outcomes)

Maintaining Infant TemperatureDuring Delivery RoomResuscitation—Intervention (NRP793)

In newborn infants (greater than 30weeks of gestation) in low-resource set-tings during and/or after resuscitation/stabilization (P), does drying and skin-to-skin contact or covering with plastic (I),compared with drying and no skin-to-skin or use of radiant warmer or in-cubator (C), change body temperature(O)?

Introduction

The ability to maintain temperature ina resource-limited setting after birth isa significant problem (see NRP 589),with a dose-dependent increase inmortality for temperatures below36.5°C. Moreover, premature infantsdemonstrated a 12-fold increase inmortality compared with term babies.Therefore, avoiding hypothermia atbirth would seem to be a relativelysimple intervention to reduce mortal-ity.


Plastic Wraps With or Without SkinDrying and Swaddling Compared WithCot or Crib With or Without Initial Useof Radiant Warmer

For the important outcome of normo-thermia or preventing hypothermiaduring resuscitation, we could not findany studies reporting on use of plasticbags. During transition (from birthto 1–2 hours after delivery), we iden-tified very-low-quality evidence (down-graded for risk of bias, inconsistency,and imprecision) from 3 randomizedclinical trials131–133 enrolling 409 new-borns of greater than 30 weeks of

gestation, showing either a reductionin incidence of hypothermia with plas-tic after drying131,132 (RR, 0.77; 95% CI,0.65–0.90) or no difference in temper-ature133 with plastic with or withoutdrying compared with cot bed or opencrib and swaddling with or withoutinitial use of radiant warmer.

Skin-to-Skin Contact Versus Cot orCrib With or Without Use of RadiantWarmer

� During transition (birth to 1–2hours after delivery), we identifiedvery-low-quality evidence (down-graded for risk of bias, indirect-ness, and imprecision) from 7randomized clinical trials134–140 en-rolling 600 newborns of greaterthan 30 weeks of gestation show-ing a reduction in the number ofbabies with hypothermia whennursed with skin-to-skin contact af-ter delivery134,136,137,140 or similarbody temperatures135,138,139 whencompared with cot or crib andswaddling with or without initialuse of radiant warmer.

Skin-to-Skin Contact Versus Incubator

For the important outcome of normo-thermia or preventing hypothermiaduring resuscitation, we could not findany studies reporting on skin-to-skincontact. During transition (birth to 1–2 hours after delivery), we identifiedvery-low-quality evidence (downgradedfor risk of bias, indirectness, and im-precision) from 2 randomized clinicaltrials136,141 enrolling 66 newborns ofgreater than 30 weeks of gestationshowing reduction in incidence of hy-pothermia by about 90%141 or a 50%reduction in drop in body tempera-ture136 with skin-to-skin contact com-pared with incubator.


There are no data examining the useof plastic wrap during resuscitation/

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stabilization. To maintain body temper-ature or prevent hypothermia duringtransition (birth to 1–2 hours of life), wesuggest that after a well newborn infantof greater than 30 weeks of gestationhas been dried, his or her trunk andlimbs may be put in a clean food-gradeplastic bag and swaddled comparedwith open crib or cot and swaddling(weak recommendation, very-low-qualityevidence).

There are no data on skin-to-skin con-tact during resuscitation/stabilization.To maintain normal body temperatureor prevent hypothermia during transi-tion (birth to 1–2 hours after delivery),we suggest well newborns of greaterthan 30 weeks of gestation be nursedwith skin-to-skin contact or kangaroomother care compared with a cot/opencrib and swaddling or incubator (weakrecommendation, very-low-quality evi-dence).


In making this suggestion on plas-tic wrap, we considered the decreasein hypothermia with plastic. How-ever, clean plastic may not be avail-able and could be costly, and useof unclean plastic may lead to in-fections.

In making this suggestion on skin-to-skin contact, we valued the pre-vention of hypothermia by using a freeand effective intervention.

An issue was raised about the qualityand thesafetyofocclusivewrap,and thesuggestion was made to include food-grade quality. The question was raisedwith regard to the availability of ther-mometers.

Knowledge Gaps

� The feasibility of skin to skin dur-ing resuscitation

� Using plastic with or without dry-ing during resuscitation

VENTILATION

The respiratory management of thenewly born infant in part depends onwhether the infant is making somerespiratory effort or not. In thebreathing term or preterm infant, ap-plication of CPAP may be sufficient toaugment endogenous effort. In the ab-sence of respiratory effort, establish-ment of FRC may be more difficult toestablish in some cases. In the terminfant, positive inflating pressure maybe sufficient to establish FRC, whereasin other cases PEEPand/or an SImay behelpful. In this section, we will reviewthe evidence for the use of CPAP in thespontaneouslybreathing infant, and theuse of SI and/or PEEP in the non-breathing infant. This section will alsoexamine the important question ofwhether a nonbreathing infant de-livered in the presence of MSAF needsto be intubated for suctioning or not.Finally, the starting oxygen concentra-tion in a premature newborn will bereviewed.

CPAP and IPPV—Intervention (NRP590)

In spontaneously breathing preterminfants with respiratory distress re-quiring respiratory support in the de-livery room (P), does the use of CPAP (I),compared with intubation and IPPV (C),improve outcome (O)?

Introduction

CPAP was introduced to neonatology inthe 1970s for treatment of respiratorydistress syndrome. However, becauseofequipment limitations, this treatmentmodality was not part of the earlyrecommendations for neonatal re-suscitation at birth. Over the past de-cade, the use of CPAP rather than theimmediate intubation and ventilationfor preterm babies who do not breathewell spontaneously after birth has beenexplored. Initially, this controversy wasalso complicated by the common

teaching that babies born very preterm(less than32weeksof gestation) shouldbe intubated electively at birth for thepurpose of administering surfactant.Therewasalso a concern that the use ofCPAP in the delivery roommight lead toa higher incidence of pneumothorax.Several randomized controlled studieshave tested these concerns, whichprompted the following2PICOanalyses.


For the critical outcome of death orbronchopulmonary dysplasia, weidentified moderate-quality evidence(downgraded for risk of bias) from 3randomized clinical trials142–144 en-rolling 2358 preterm infants born atless than 30 weeks of gestation show-ing potential benefit to starting treat-ment with CPAP in the first 15 minutesafter birth (RR, 0.91; 95% CI, 0.83–1.00).

For the critical outcome of death, weidentified moderate-quality evidence(downgraded for risk of bias, impreci-sion) from the same 3 randomizedclinical trials142–144 showing no benefitto starting treatment with CPAP (RR,0.82; 95% CI, 0.66–1.03). However, werecognize that while the point estimatewould suggest potential for benefit, theconfidence intervals cross unity to 1.03,suggesting that the potential for harmis minimal.

For the critical outcome of broncho-pulmonary dysplasia, we identifiedmoderate-quality evidence (down-graded for indirectness) from thesame 3 randomized clinical trials142–144

showing no benefit to starting treat-ment with CPAP (RR, 0.92; 95% CI,0.82–1.03). However, we recognize thatwhile the point estimate would suggestpotential for benefit, the confidenceintervals cross unity to 1.03, suggestingthat the potential for harm is minimal.

For the critical outcome of air leak, weidentified very-low-quality evidence(downgraded for inconsistency andvery serious imprecision) from the




same 3 randomized clinical trials142–144

showing no benefit to starting treat-ment with CPAP (RR, 1.24; 95% CI, 0.91–1.69).

For the critical outcome of severe IVH,we identified very-low-quality evidence(downgraded for inconsistency andserious imprecision) from the same 3randomized clinical trials142–144 show-ing no benefit to starting treatmentwith CPAP (RR, 1.09; 95% CI, 0.86–1.39).

For the important outcome of necro-tizing enterocolitis, we identifiedmoderate-quality evidence (down-graded for imprecision) from the same3 randomized clinical trials142–144

showing no benefit to starting treat-ment with CPAP (RR, 1.19; 95% CI, 0.92–1.55).

For the important outcome of severeretinopathy of prematurity, weidentified low-quality evidence (down-graded for very serious imprecision)from 2 randomized clinical trials143,144

enrolling 1359 infants showing nobenefit to starting treatment with CPAP(RR, 1.03; 95% CI, 0.77–1.39).


For spontaneously breathing preterminfants with respiratory distress re-quiring respiratory support in the de-livery room, we suggest initial useof CPAP rather than intubation andIPPV (weak recommendation,moderate-quality evidence).


Inmaking this suggestion,we recognizethat the absolute reduction in risk ofadverse outcome associated withstarting with CPAP is small and thatinfants recruited to the trials had a highrate of treatment with antenatal ste-roids but we value the less invasiveapproach.

CPAP was introduced in the 2010CoSTR13–15 as an option to be con-sidered for babies who are breathing,

but breathing with difficulty. The pre-vious recommendation had been tosimply administer blow-by oxygen.The current PICO question did notaddress the option of using no sup-port. There was a consensus that, inthe absence of contrary evidence,administration of CPAP, with or with-out supplementary targeted oxygen,is preferable in this situation if resour-ces permit.

Knowledge Gaps

� The balance of risks and benefitsof this approach in infants whohave not received antenatal ste-roids is unknown.

� A further trial of CPAP versus in-tubation and IPPV in high-risk pre-term infants at lower gestations isrequired to determine the risksand benefits more clearly. It isnot clear whether there is a signif-icant effect on mortality. The CIsfor the other morbidities of prema-turity leave open the possibilitythat any benefit in relation to bron-chopulmonary dysplasia might stillbe balanced by a small increase inrisk of severe IVH or necrotizingenterocolitis.

� The utility of using an intubation-surfactant-extubation sequence(INSURE) approach145 to facilitateearly stabilization on CPAP soon af-ter birth has been compared withCPAP alone in at least 2 trials. Thisshould be the subject of a futureworksheet.

Ventilation Strategies in theDelivery Room

The most effective method for estab-lishing an FRC in the fluid-filled lung ofa newborn who does not breathespontaneously has been debated formanydecades. In the1980s, Vyaset al146

suggested a technique of administer-ing an SI of up to 5 seconds in duration.Both standard IPPV with or without

PEEP and inflation breaths up to 3seconds in duration are currently ini-tial strategies advocated to initiateventilation (Neonatal Resuscitation Pro-gram, European Resuscitation Council).Several recent animal studies havesuggested that a longer SI may be ben-eficial for short-term respiratory out-comes. The following 3 PICO analysesreflect an in-depth analysis of the dif-ferent strategies that have been sug-gested for this initial establishment ofFRC after birth.

Sustained Inflations—Intervention(NRP 809)

In term and preterm newborn infantswho do not establish spontaneousrespiration at birth (P), does adminis-tration of 1 or more pressure-limitedsustained lung inflations (I), com-pared with intermittent PPV with shortinspiratory times (C), change Apgarscore at 5 minutes, establishment ofFRC, requirement for mechanical ven-tilation in first 72 hours, time to heartrate greater than 100/min, rate of tra-cheal intubation, overall mortality (O)?


For the critical outcome of need formechanical ventilation in the first 72hours after birth, low-quality evidence(downgraded for inconsistency, in-directness, and imprecision) from 3randomized clinical trials enrolling 404newborns showed significant benefit ofsustained lung inflations.18,147,148 Inaddition, very-low-quality evidence (down-graded for variability of interventions inSI and control populations) from 2 co-hort studies with a total of 331 patientsalso showed benefit of sustained lunginflations as compared with intermittentPPV with short inspiratory times.18,149

One randomized clinical trial151 wasexcluded from analysis due to meth-odological concerns pertaining to dif-ferences in the various interventionsbetween the study groups of which sus-tained lung inflation was merely one.

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For the critical outcome of mortality,low-quality evidence (downgraded forindirectness and imprecision) from 3randomized clinical trials enrolling 404newborns18,147,149 and very-low-qualityevidence (downgraded for variability ofinterventions in sustained lung in-flation and control populations) from 2cohort studies with a total of 331patients showed no benefit as com-pared with IPPV with short inspiratorytimes.18,147,149

For the critical outcome of broncho-pulmonary dysplasia, low-quality ev-idence (downgraded for inconsistency,indirectness, and imprecision) from 3randomized clinical trials enrolling 404patients showed no benefit.18,147,149

Very-low-quality evidence (downgradedfor variability of interventions in SIand control populations) from 2 co-hort studies with a total of 331patients showed significant benefitof sustained lung inflations as com-pared with IPPV with short inspiratorytimes.18,149

For the critical outcome of air leak,low-quality evidence (downgraded forinconsistency, indirectness, and im-precision) from 3 randomized clinicaltrials enrolling 404 newborns18,147,148

and very-low-quality evidence (down-graded for variability of interventionsin SI and control populations) from 2cohort studies with a total of 331patients showed no effect of sus-tained lung inflation as comparedwith IPPV with short inspiratorytimes.147,148

For the important outcome of Apgarscore, there was no difference betweengroups in any studies reviewed.18,147,148,149

For the important outcome of need forintubation, very-low-quality evidence(downgraded for lack of controls) from1 cohort study18 showed that the needin the delivery room was significantlylower in infants who received an SIcompared with conventional manage-ment.

For the important outcome of heartrate greater than 100/min, no evi-dence was found.

For the important outcome of estab-lishment of FRC, no evidencewas found.

For the important outcome of Fio2 in thedelivery room, no evidence was found.

For the important outcome of chestcompressions in the delivery room,no evidence was found.

Additional comments:

� No human studies evaluated timeto heart rate greater than 100/min,establishment of FRC, Fio2 in thedelivery room, or need for chestcompressions in the delivery room.

� In a small case series of 9 asphyx-iated term infants (very-low-qualityevidence), a prolonged initial infla-tion of 5 seconds produced a 2-foldincrease in FRC compared with his-toric controls.146

� Comparison of all studies (ran-domized clinical trials and cohort)was compromised due to the het-erogeneity of methodology, ie, widedifferences in duration of the ini-tial SI (5–20 seconds) as well asthe peak inspiratory pressure(20–30 cm H2O) and use of a varietyof interface devices to deliver theSI (endotracheal tube, face mask,or nasopharyngeal tube). Threestudies repeated the initial sus-tained lung inflation once,18,149,150

1 at a higher positive inflatingpressure,18 whereas 1 study re-peated the SI twice with increasingpositive inflating pressure.148

� No studies compared the efficacyof a single SI with multiple SIs.

� Animal studies of the effects ofSI on alveolar recruitment haveshown in lambs151 and pretermrabbits152 more uniform lung infla-tion and better lung compliance, ifanimals received an SI before ini-tiation of mechanical ventilation.

However, a study by Klopping-Kete-laars153 showed no benefit after aninitial SI in preterm lambs, and an-other study showed that stepwiseincreases in PEEP resulted in bet-ter overall lung mechanics thantreatment with an initial SI.154


We suggest against the routine useof initial SI (greater than 5 secondsduration) for preterm infants withoutspontaneous respirations immedi-ately after birth, but an SI may beconsidered in individual clinical cir-cumstances or research settings(weak recommendation, low-qualityevidence).


In making this recommendation, and inthe absence of long-term benefits, weplace a higher value on the negativeaspect involving lack of clarity as to howto administer sustained lung inflationsversus the positive findings of a re-duced need for intubation at 72 hours.

Although the studies reviewed showedthat administration of an SI reduced theneed for mechanical ventilation in thefirst 72 hours of life, the use of SI did notchange the incidenceof important long-termoutcomes related to lung function,including risk of bronchopulmonarydysplasia or overall mortality. Studiesthus far are likely underpowered forthese outcomes.

Therewasmuchdebateabout theuseofSI. The methods used in delivering SIvaried among studies. It was stressedthat different devices varied in theirability to generate pharyngeal pressures.Moreover,arecentanimalstudysuggeststhat there may be unintended glottisclosure associated with SI. There wasalso concern that the current wording ofthe treatment recommendation may beviewed by some as limiting the potentialfor future clinical studies.


Evidence evaluators were asked to de-cide whether to include the te Pas ar-ticle.155 The decision was made toexclude it because of multiple con-founding interventions. It was thoughtthat more detail in the consensus onscience was needed to reflect thatstudies used SI ranging from 5 to 25seconds. There was debate about theuse of the wording suggest against.Several members were in favor of us-ing this term, because there is in-sufficient evidence regarding how toadminister sustained lung inflation,how many such breaths should be ap-plied, or whether it should be used withor without PEEP. It is difficult to ex-trapolate from animal data, becausethe animals in the studies were non-breathing and had tracheostomies,so that the anatomy, physics, andphysiology are different. Althoughthere was consensus agreement onthe current wording, it was notedthat individual councils may chooseto interpret the recommendationsdifferently.

Knowledge Gaps

� The duration of an SI, the appropri-ate peak initial inflation pressure,the number of SIs to be adminis-tered, and an early measure of re-sponse remain unclear.

� Further studies are essential to de-termine the optimal pressure andduration of SI that would allow theestablishment of FRC while mini-mizing the risk of barotrauma inthe newly born infant and long-term morbidity.

Outcomes for PEEP Versus No PEEPin the Delivery Room—Intervention(NRP 897)

In preterm/term newborn infants whodonot establish respiration at birth (P),does the use of PEEPaspart of the initialventilation strategy (I), compared withno PEEP (C), improve Apgar score at

5 minutes, intubation in the deliveryroom, chest compressions in the de-livery room, heart rate greater than100/min by 2 minutes of life, time forheart rate to rise above 100/min, airleaks, oxygen saturation/oxygenation,Fio2 in the delivery room, mechanicalventilation in the first 72 hours, bron-chopulmonary dysplasia, survival todischarge (O)?

Introduction

In the 2010 CoSTR, new recommenda-tions were introduced regarding theuse of CPAP for babies exhibitingbreathing difficulty and for using PEEPwhenever IPPV was required. Butproblemshave continued because of aninability of self-inflating bags to reliablydeliver PEEP, and self-inflating bags arethe most common devices used forneonatal resuscitation worldwide. ThisPICO question and the one immediatelyfollowing (NRP 870) were constructedto examine the value of using one de-vice over another and the need for PEEPwhen administering IPPV during re-suscitation.


For the critical outcome of mortalitybefore discharge, we identified low-quality evidence from 2 randomizedtrials of 596 preterm newborns show-ing no benefit (RR, 0.616; 95% CI, 0.274–1.382) to providing PEEP comparedwith no PEEP (downgraded for seriousimprecision and risk of bias).156,157

For the critical outcome of chroniclung disease, we identified moderate-quality evidence from 2 randomizedtrials of 596 preterm newborns show-ing no benefit (RR, 1.153; 95% CI, 0.711–1.871) to providing PEEP as comparedwith no PEEP (downgraded for impre-cision and risk of bias).156,157

For the critical outcome of need forcardiac drugs or chest com-pressions in the delivery room, weidentified low-quality evidence from 2

randomized trials of 596 pretermnewborns showing no benefit (RR,1.468; 95% CI, 0.550–3.917) to providingPEEP as compared with no PEEP156,157

(downgraded for imprecision and riskof bias).

For the important outcome of oxygensaturation at 5 minutes after birth,we identified moderate-quality evi-dence from 1 randomized trial of 80preterm newborns showing no benefit(P50.55) to providing PEEP (medianSpo2, 49%; interquartile range [IQR],25%–90%) versus not providing PEEP(median Spo2, 59%; IQR, 33%–66%)(downgraded for imprecision and riskof bias).156

For the important outcome of maxi-mum concentration of oxygen usedduring resuscitation, we identifiedlow-quality evidence from 1 random-ized trial of 516 preterm newbornsshowing moderate benefit (P50.005)to providing PEEP (mean, 48%; stan-dard deviation [SD], 0.2) versus notproviding PEEP (mean, 53%; SD, 0.2).157

For the important outcome of heartrate greater than 100/min at 2minutes of age, we identified low-quality evidence from 1 randomizedtrial of 516 preterm newborns showingno benefit to providing PEEP versus notproviding PEEP (RR, 1.656; 95% CI,0.938–2.923) (downgraded for impre-cision and risk of bias).157

For the important outcome of time forheart rate to rise to greater than100/min, we identified moderate-quality evidence from 1 randomizedtrial of 516 preterm newborns showingno benefit to providing PEEP (median,1 minute; IQR, 0.5–1.8) versus not pro-viding PEEP (median, 1minute; IQR, 0.5–1.9) (downgraded for imprecision andrisk of bias).157

For the important outcome of need forintubation in the delivery room, weidentified moderate-quality evidencefrom 2 randomized trials of 596

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preterm newborns showing no benefit(RR, 1.208; 95% CI, 0.907–1.609) toproviding PEEP (downgraded for im-precision and risk of bias)156,157 versusnot providing PEEP.

For the important outcome of need formechanical ventilation in the first72 hours, we identified low-qualityevidence from 1 randomized trial of80 preterm newborns showing nobenefit (RR, 0.317; 95% CI, 0.093–1.086)to providing PEEP (downgraded forimprecision and risk of bias) versusnot providing PEEP. We identified only 1randomized clinical trial that includedterm infants,157 which provided in-sufficient data to address this questionas a secondary outcome measure ina subgroup analysis (very-low-qualityevidence, downgraded for serious im-precision and risk of bias).

For the important outcome of pulmo-nary air leaks, we identified low-quality evidence from 2 randomizedtrials of 596 preterm newborns show-ing no benefit (RR, 1.401; 95% CI, 0.414–4.735) to providing PEEP (downgradedfor imprecision and risk of bias)156,157

versus not providing PEEP.

For the important outcome of Apgarscore less than 6 at 5 minutes, weidentified moderate-quality evidencefrom 1 randomized trial of 516 pretermnewborns showing no benefit to pro-viding PEEP (RR, 0.813; 95% CI, 0.472–1.402) (downgraded for imprecisionand risk of bias)157 versus not pro-viding PEEP.

For the less-important outcome of Apgarscore at 5 minutes, we identifiedmoderate-quality evidence from 1 ran-domized trial of 80 preterm newbornsshowing no benefit (P50.18) to providingPEEP (median, 7; IQR, 6–8) versus no PEEP(median, 7; IQR, 6–9) (downgraded forimprecision and risk of bias).156


We suggest using PEEP ventilation forpremature newborns during delivery

room resuscitation (weak recommen-dation, low-quality evidence).

We cannot make any recommendationfor term infants because of insufficientdata.


In making this suggestion, we areconsidering the small reduction inmaximum oxygen concentration neededduring resuscitation with 5 cmH2O PEEPcomparedwith those not receiving PEEPshown in 1 human study, and consid-ering the evidence from animal studies(see NRP 809). Interpretation of humanstudies is further complicated by vary-ing interfaces (eg, face mask versusendotracheal tube) and methods ofgenerating PEEP (eg, self-inflating bagswith PEEP valve versus T-piece re-suscitator).

Only 1 study was available to indirectlyaddress the specific PICO question,157

where a subgroup comparison wasapplied. Good animal studies areavailable but are classified as low lev-els of evidence from the point of ap-plicability due to indirectness (see NRP809). There was concern that the evi-dence based on the GRADE criteria wasregarded as low quality. There wasa major struggle to come up witha recommendation when the evidencewas weak. The only positive effectfound was a 5% change in Fio2 (seecomments after NRP 870).

Knowledge Gaps

� Properly powered, well-designedrandomized trials specificallyaddressing important outcomesfor the effects of PEEP in the de-livery room are necessary.

� It remains unclear as to the opti-mal level of PEEP to use.

� The question of static PEEP versusdynamic PEEP needs to be delin-eated.

� Differential effects of PEEP at dif-ferent gestational ages and for dif-ferent pathologies remain to bedetermined.

T-Piece Resuscitator and Self-Inflating Bag—Intervention (NRP870)

In newborns (preterm and term) re-ceiving ventilation (PPV) during re-suscitation (P), does using a T-pieceresuscitator with PEEP (I), comparedwith using a self-inflating bag withoutPEEP (C), achieve spontaneous breath-ing sooner and/or reduce the incidenceof pneumothorax, bronchopulmonarydysplasia, and mortality (O)?

Introduction

The T-piece resuscitator has replacedthe self-inflating and flow-inflating bagin many institutions. One major reasonfor this change has been the inability ofthe self-inflating bag to deliver eitherCPAP or PEEP reliably. Advantages of theT-piece include ease of use and ability todeliver CPAP, PEEP, and/or IPPV. How-ever, it also requires a pressurized-gassource to drive the device. This PICOquestion is intended to review the evi-dence of the utility of self-inflating bagsversus T-piece resuscitators.


For the following consensus on sciencestatements, the analysis is based on allpatients (n580) from 1 study156 andfrom a subgroup analysis (n5453) ina second study.157

For the critical outcome of death be-fore discharge, we identified low-quality evidence (downgraded for riskof bias and imprecision) from 2 ran-domized clinical trials156,157 enrolling532 patients showing no benefit to theuse of a T-piece resuscitator as com-paredwith a self-inflating bag (OR, 0.68;95% CI, 0.31–1.56).

For the critical outcome of broncho-pulmonary dysplasia, which was only





















assessed for infants of less than 1500 g,we identified low-quality evidence(downgraded for risk of bias and im-precision) from 2 randomized clinicaltrials156,157 enrolling 151 patientsshowing no benefit to the use T-pieceresuscitator as compared with self-inflating bag (OR, 0.92; 95% CI, 0.59–1.43).

For the critical outcome of air leaks,we identified low-quality evidence(downgraded for risk of bias and im-precision) from 2 randomized con-trolled trials156,157 enrolling 532patients showing no benefit to the useof T-piece resuscitator as comparedwith self-inflating bag (OR, 1.72; 95% CI,0.51–5.78).

For the important outcome of achiev-ing spontaneous breathing or re-ducing intubation in delivery room,we identified very-low-quality evidence(downgraded for risk of bias, impreci-sion, and inconsistency) from 2 ran-domized clinical trials156,157 enrolling532 patients showing no benefit to theuse of T-piece resuscitator as com-pared with self-inflating bag (OR, 0.80;95% CI, 0.59–1.07).


There is insufficient evidence, so therecommendation of one device overanother would be purely speculativebecause the confidence in effect esti-mates is so low.


The current studies suggest a benefit tousingPEEP toassist establishmentof anFRC during transition of the fluid-filledlung to an air-breathing organ. How-ever, the evidence to date is not suffi-ciently compelling to recommendagainst using a self-inflating bag (inwhich reliable administration of PEEP isnot achievable with current devices)during neonatal resuscitation, partic-ularly in regions where pressurized

gases are not readily available. PEEP isrecommended when the facilities andequipment permit it to be given reliably(approximately 5 cm H2O).

Knowledge Gaps

� One cluster randomized controlledtrial157 showed benefit of using T-piece resuscitator for achievingspontaneous breathing in the latepreterm (mean gestational age36 weeks) population. Further re-search in this population would beimportant.

� There are no studies comparingthe flow-inflating bag to either theself-inflating bag or the T-piece re-suscitator (with or without PEEP)for neonatal resuscitation. Theo-retically, the flow-inflating bagshould be similar to the T-pieceresuscitator, although ease ofuse may prove it to be less effec-tive.

� Studies comparing the flow-inflating bag to the other 2 deviceswould be helpful.

Intubation and Tracheal Suctioningin Nonvigorous Infants BornThough MSAF Versus No Intubationfor Tracheal Suctioning—Intervention (NRP 865)

In nonvigorous infants at birth bornthrough MSAF (P), does tracheal in-tubation for suctioning (I), comparedwith no tracheal intubation (C), reducemeconium syndrome or prevent death(O)?

Introduction

For more than 30 years, it has beenrecommended that newborns withMSAF should receive endotracheal in-tubation,with tracheal suctioningusingthe endotracheal tube as a suctiondevice. Approximately 15 years ago, asa result of a multicenter randomizedclinical trial, the recommendation was

restricted to babies who appeared tohave respiratory compromise at birth(ie, were nonvigorous). It remainscontroversial as to whether even non-vigorous babies benefit from this pro-cedure. This PICO question is intendedto address this issue.


For the critical outcome of mortalityand/or meconium aspiration syn-drome (MAS), we identified 1 ran-domized study involving 122 infants(low-quality evidence, downgraded forrisk of bias and imprecision)17 com-paring tracheal intubation for suc-tioning versus no tracheal intubationfor suctioning in nonvigorous infantsshowing no benefit to suctioning in ei-ther reduced mortality and/or MAS.

For the critical outcome of mortalityand/or MAS, we identified very-low-quality evidence from 3 studies158–160

including 12 389 MSAF infants showinghigher incidence of MAS in depressedinfants (268/1022, 26%) who had tra-cheal intubation for suctioning com-pared with vigorous infants (34/11 367,0.3%) who were not intubated (down-graded for indirectness).

For the critical outcome of mortalityand/or MAS, we identified evidencefrom 7 very-low-quality observationalstudies161–167 demonstrating improvedsurvival and lower incidence of MASwhen infants (including depressedand/or vigorous infants) born throughMSAF were intubated for tracheal suc-tioning (downgraded for indirectnessand inconsistency).

For the critical outcome of mortalityand/or MAS, we identified evidencefrom 9 very-low-quality observationalstudies158–160,168–173 demonstrating noimprovement in survival and/or in-cidence of MAS (including depressedand/or vigorous infants) when infantsborn through MSAF were intubated fortracheal suctioning (downgraded forindirectness).

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There is insufficient published humanevidence to suggest routine trachealintubation for suctioning of meconiumin nonvigorous infants born throughMSAF as opposed to no tracheal in-tubation for suctioning.


In making this suggestion, we placevalueonbothharmavoidance(delays inproviding bag-mask ventilation, poten-tial harm of the procedure) and theunknown benefit of the intervention ofroutine tracheal intubation and suc-tioning.

Routine suctioning of nonvigorousinfants is more likely to result indelays in initiating ventilation, espe-cially where the provider is unable topromptly intubate the infant or suctionattempts are repeated. In the absenceof evidence of benefit for suctioning, theemphasis should be on initiating ven-tilation within the first minute of life innonbreathing or ineffectively breathinginfants.

Much of the deliberations focused onthe wording of the treatment recom-mendation. There were 3 differenttreatment recommendation options.First “We suggest against the routineintubation of nonvigorous infants bornthrough MSAF.” Second “We suggestthat routine tracheal intubation forsuctioning of meconium in nonvigorousinfants should not be considered asa standard of care but may be consid-ered a reasonable alternative to notracheal intubation in some settings.”Third “We suggest that routine trachealintubation for suctioning of meconiumin nonvigorous infants should not beconsidered as a standard of care butmay be considered a reasonable alter-native to no tracheal intubation if a me-conium plug is suspected.” There wasconcern that the legal profession couldmisinterpret the term standard of care.

Consensus was reached on the finaltreatment recommendation.

Knowledge Gaps

� Tracheal intubation or no trachealintubation for suctioning in non-vigorous infants: Is there a benefitor harm?

Oxygen Concentration forResuscitating Premature Newborns—Intervention (NRP 864)

Amongpretermnewborns (less than 37weeks of gestation) who receive PPV inthe delivery room (P), does the use ofhigh O2 (50%–100%) as the ventilationgas (I), compared with low concen-trations of O2 (21%–30%) (C), decreasemortality, decrease bronchopulmo-nary dysplasia, decrease retinopathy,decrease IVH (O)?

Introduction

The fact that high oxygen concentrationscan be toxic to the newly born lungs hasbeen recognized in all CoSTR statementssince 2000. The original studies exam-ined only 21% oxygen versus 100% andled to a recommendation that blendedoxygen be used to titrate the concen-tration to achieve an oxygen saturationthat is reflective of what healthy babiesborn at term experience (ie, targetedsaturation). There has been an ongoingcontroversy as towhat the initial oxygenconcentration should be. Babies born atterm should be started in air (21%), butthere has been uncertainty as towhether the preterm baby should bestarted in a high concentration (50%–100%) versus low concentration (21%–30%) of oxygen while the pulse oximetryis being attached. This PICO questionwas intended to examine only thestarting concentration of administeredoxygen, not the targets.


For the critical outcome of mortalitybefore discharge, we found moderate-

quality evidence from 7 randomizedclinical trials enrolling 607 subjectsshowing no benefit to beginning re-suscitation with high-oxygen as com-pared with low-oxygen concentration(RR, 1.48; 95%CI, 0.8–2.73). The quality ofevidence was downgraded for impreci-sion.174–180 When limited to randomizedclinical trials with concealed alloca-tion and oxygen targeting as a coin-tervention, we found moderate-qualityevidence from 5 trials enrolling 468subjects showing no benefit to begin-ning resuscitation with a high-oxygenconcentration as compared with low-oxygen concentration (RR, 1.33; 95% CI,0.68–2.62). The quality of evidence wasdowngraded for imprecision.175,177–180

We found very-low-quality evidencefrom 1 cohort study including 125 sub-jects showing no benefit to beginningresuscitation with high-oxygen as com-pared with low-oxygen concentration(RR, 1.31; 95% CI, 0.41–4.24). The qualityof evidence was downgraded for seri-ous imprecision.181

For the critical outcome of broncho-pulmonary dysplasia, we found low-quality evidence from 5 randomizedtrials enrolling 502 subjects showingno benefit to beginning resuscitationwith a high-oxygen as compared withlow-oxygen concentration (RR, 1.08;95% CI, 0.59–1.98). The quality of evi-dencewasdowngraded for inconsistencyand imprecision.175,177–180

For the critical outcome of intra-ventricular hemorrhage, we foundmoderate-quality evidence from 4 ran-domized clinical trials enrolling 400subjects showing no benefit to begin-ning resuscitation with a high-oxygenas compared with low-oxygen concen-tration (RR, 0.90; 95% CI, 0.47–1.72). Thequality of evidence was downgradedfor imprecision.175,178–180

For the important outcome of reti-nopathy of prematurity, we foundmoderate-quality evidence from 3 ran-domized trials enrolling 359 subjects



showing no benefit to beginning re-suscitation with a high- as comparedwith low-oxygen concentration (RR,1.28; 95% CI, 0.59–2.77). The quality ofevidence was downgraded for impre-cision.175,178,179


We recommend against initiating re-suscitation of preterm newborns (lessthan 35 weeks of gestation) with highsupplementary oxygen concentrations(65%–100%).

We recommend initiating resuscitationwith a low-oxygen concentration (21%–30%) (strong recommendation,moderate-quality evidence).


In making this recommendation, weplace value on not exposing pretermnewborns to additional oxygen withoutproven benefit for critical or importantoutcomes. Our preference for eachoutcome, therefore,was to describe therisk of high-oxygen relative to low-oxygen concentration. In all studies,irrespective of whether air or high ox-ygen including 100% was used to initi-ate resuscitation, by the time ofstabilization most infants were in ap-proximately 30% oxygen. We recognizethat all but 1 included study allowedadjustment of oxygen concentrationbased on pulse oximetry and/or heartrate response.

Concerns were expressed about thepractical implications of recommend-ing separate and simultaneous moni-toring of both heart rate and oxygensaturation, although accurate meas-urements of both variables are im-portant (see NRP 898). The chosenrange for the low oxygen startingpoint (21%–30%) was also ques-tioned, but the available articles de-fined it. Whether the high oxygenshould be greater than 60% was alsodiscussed.

Knowledge Gaps

� The most appropriate time-specificoxygen targets for premature new-borns need to be defined.

� Neurodevelopmental outcomes forpreterm newborns resuscitatedwith low- and high-oxygen concen-trations need to be determined.

CIRCULATORY SUPPORT

Circulatory support focused on themost effective method of deliveringchest compressions and includedcomparison of the 2-thumb versus the2-finger techniques as well as com-paring various compression-to-ventilation ratios. During the evidenceevaluation in 2010, it was decided tocontinue recommending a chest com-pression–to–ventilation ratio of 3:1 asopposed to 15:2 or 30:2, predominantlybecause profound bradycardia orasystole in the newly born period isinvariably secondary to an asphyxialrather than a primary cardiac event.Evidence in this review was sought todetermine whether there was any re-cent evidence to change this recom-mendation. Moreover, factors importantto the ergonomics of CPR for enhancingblood flow during chest compressionswere identified. The evidence belowsummarizes these findings.

2-Thumb Versus 2-FingerTechniques for Chest Compression—Intervention (NRP 605)

In neonates receiving cardiac com-pressions (P), does the useof a 2-thumbtechnique (I), compared with a 2-fingertechnique (C), result in return ofspontaneous circulation (ROSC), im-proved neurologic outcomes, improvedsurvival, improved perfusion and gasexchange during CPR, and decreasedcompressor fatigue (O)?

Introduction

Two different techniques for adminis-tering chest compressions during re-

suscitation of neonates have beensuggested: 2 thumbs, with fingerssurrounding the lateral and posteriorchest, versus 2 fingers placed verticallyon the lower sternum. This PICO ques-tion is intended to evaluate whichtechnique is preferable.


For the critical outcomes of time toROSC, survival rates, or neurologicinjury, we found no data.

For the critical outcome of improvedperfusion and gas exchange duringCPR, we identified low-quality evidencefrom 9 randomized controlled trials(downgraded for indirectness andimprecision)182–190 and 6 nonrando-mized controlled trials (downgradedfor indirectness, imprecision, andhigh risk of bias)191–196 identifyinghigher blood pressure generationwith the 2-thumb versus the 2-fingermethod.

For the important outcome of com-pressor fatigue, we identified low-quality evidence from 4 randomizedcontrolled trials (downgraded for in-directness and imprecision), with2183,197 identifying less fatigue with the2-thumb versus the 2-finger technique,and 2 studies finding no differ-ence.189,198

New compression methods:

� Thumb and index finger (TIF)199

compared the new method versusthe 2-thumb and 2-finger methodson manikins. Cardiac compres-sions lasted for only 5 minuteswhile recording rate, hand loca-tion, depth, incomplete recoil, ex-cessive depth, and error rateduring CPR. Two-thumb and TIFhad less decay in “suitable chestcompressions” over the 5 minutescompared with the 2-fingermethod.

� Adhesive glove200 compared us-ing the adhesive glove with conven-tional CPR in 4 groups, including

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an infant group in a manikinmodel. The 2-thumb method wasused as standard in the infantgroup versus adhesive 2-thumbmethod. The theory is that theglove enables active compression-decompression. Rate, compres-sion, and decompression depthwere measured. No differences infatigue variables were found amongstgroups. Results showed more ac-tive decompression with the adhe-sive glove group.

Summary: No evidence was foundsupporting the new thumb and indexfinger technique as superior to the 2-thumb method. The adhesive gloveenhanced active decompression butdid not reduce fatigue.

Other issues:

� Does the CPR technique causefractures? Franke201 performeda 10-year retrospective surveyto determine whether the 2-thumb technique causes rib frac-tures. All infants received CPRplus chest x-rays. Median agewas 9 days.

Summary: There was no evidence ofrib fractures in any case.

� Best location on the sternum:Using 4 assessment methods overa wide age range of infants,202 itwas confirmed that the heart liesunder the lower third of the ster-num. In addition, blood pressurereadings were higher when car-diac compressions were appliedto the lower versus the middlethird of the sternum. Use of theinfant computed tomography (CT)scan data (mean age, 4.4 months)and adult thumb side-by-sidemeasurements on manikins203 con-firmed that the left ventricle liesmostly under the lower quarterof the sternum. No functional datawere collected to confirm betteroutcomes if compressions focused

on that area. An assumption wasmade that the lower third of thesternum was the best position forcompressions.204

� Term and preterm babies: Cor-rect positioning on the chest wasdetermined to be much better withthe 2-thumb method in bothgroups of babies, although incor-rect placements were found forboth techniques in infants lessthan 1500 g. Chest x-ray analysisof term and preterm babies205

found the heart to be under thelower third of the sternum. ChestCT scans of infants (mean age, 4.7months), compared with adultthumb measurements on a mani-kin, comparing the 2-thumbmethod side by side or superim-posed,206 demonstrated that theside-by-side method increases thelikelihood of other organs (lungsand liver) being under the pointsof compressions application. Amanikin study looked at fatiguelevels with the 2-thumb technique,comparing side-by-side or super-imposed thumb position207 demon-strated that the superimposedthumb technique generated highersimulated blood pressure andpulse pressure but had a higherfatigue-rating score. Physiologic in-dices of fatigue showed no differ-ence between groups. CT scansof the chest to compare thumb(side-by-side)/fingers measurementsplaced on manikins were con-ducted to determine which methodavoided compressing other struc-tures when using the lower thirdof the sternum.208 Both methodscompress other structures, butthe 2-thumb method (side-by-side)performs better than the two fin-ger method. The accuracy of usingthe nipple line to the xiphisternumlandmarks for 2-finger chest com-pression was examined by Clem-

ents.209 They concluded that thismethod could result in abdomenand xiphisternum compression inall infants and suggested an alter-nate method of determining posi-tion.

Summary: The lower one third of thesternum remains the best location topress over the newborn heart. Super-imposed thumbs may be the bettertechnique.


We suggest that chest compressions inthe newborn should be delivered bythe 2-thumb, hands-encircling-the-chestmethod as the preferred option (weakrecommendation, very-low-quality evi-dence).

We suggest that chest compressionsshouldbedeliveredover the lower thirdof the sternum(weak recommendation,very-low-quality evidence).


None are noted.

Knowledge Gaps

� No studies of any kind regardingthe most critical outcomes wereavailable.

� No data from good transitionalmodels were found.

� There are very limited human neo-natal data.

Chest Compression Ratio—Intervention (NRP 895)

In neonates receiving cardiac com-pressions (P), do other ratios (5:1, 9:3,15:2, synchronous, etc) (I), comparedwith 3:1 compressions to ventilations(C), increase survival rates, improveneurologic outcomes, improve perfu-sion and gas exchange during CPR,decrease time to ROSC, decrease tissueinjury, or decrease compressor fatigue(O)?



Introduction

Chest compressions administered ina ratio of 3 compressions to 1 ventila-tion have been recommended for re-suscitation of neonates at birth. Theconcept has been that newborns arebornwith lungsfilledwithfluid,muchofwhich is absorbed directly across thealveolar membrane with the first fewbreaths. If a newborn is compromisedsufficiently to prevent spontaneousbreathing, resulting in bradycardia orcardiac arrest, successful resus-citation must achieve adequate lungaeration and ventilation to reverse anasphyxial pathophysiology. Thus, thefocus of newborn resuscitation effortsmustbeprimarilyaimedatestablishingventilation first and cardiac supportsecond. This PICO question is meant toidentifywhichcompression-to-ventilationratio will be most effective at achievingthis.


Animal studies demonstrate no advan-tage tohighercompression-to-ventilationratios (very-low-quality evidence, down-graded for potential bias, indirectness,and imprecision) regarding

� Short-term survival (2 random-ized controlled trials including54 pigs)210,211

� Gas exchange during CPR (2 ran-domized controlled trials including54 pigs)210,211

� Time to ROSC (2 randomizedcontrolled trials including 54pigs)210,211

� Markers of tissue injury (lung/brain) (2 randomized controlledtrials including 54 pigs)212,213

There was no evidence identified toaddress the critical issue of neuro-logic outcome.

Manikin studies demonstrated a disadvan-tage to higher compression-to-ventilationratios (5:1, 9:3, 15:2) (very-low-qualityevidence, downgraded for potential

bias, imprecision, and indirectness)with regard to

� Compressor fatigue (betterdepth of compression, less decayin depth over time; 1 randomizedcontrolled trial including 32 resus-citation providers)214

� Minute ventilation (1 randomizedcontrolled trial including 32 resus-citation providers)214

� A single manikin study demon-strated higher minute ventilationfor asynchronous compressions(120 compressions: 40 ventila-tions) compared with 3:1 (90 com-pressions: 30 ventilations) (1randomized controlled trial includ-ing 2 resuscitation providers with5 different sessions per treatmentarm)215


We suggest continued use of a 3:1compression-to-ventilation ratio forneonatal CPR (weak recommendation,very-low-quality evidence).


We prefer to retain our prior recom-mendation of 3:1 compression-to-ventilation ratio for neonatal CPR,because there is no compelling evi-dence suggesting a benefit to otherratios for thenewborn. Since asphyxiais the predominant cause of cardio-vascular collapse in the newborn,effective resuscitation requires sig-nificant focus on ventilation. In addi-tion, we value consistency in theresuscitation algorithm and educa-tion programs unless new evidencedrives the change.

All studies were done in young post-transitioned piglets (no human or ani-mal data in a transitioning model).Since there is no evidence in eithera human or animal with fluid-filledlungs, we need to be clear when com-municating with other groups (pediat-

rics and basic life support providers)that neonates have unique cardiopul-monary physiology, prompting ourunique 3:1 ratio.

Somemay not agree, but the values andpreferences statement expresses whywe still favor a 3:1 ratio.

Knowledge Gaps

� Specific research is required, suchas clinical and appropriate animalmodel studies.

� We need neonatal human data.

� How many compressions in a roware required to achieve forwardblood flow and adequate coronaryperfusion pressure during new-born asphyxial arrest?

� How many interposed ventilationsare needed to achieve and main-tain normocapnia during cardiaccompressions due to newbornasphyxial arrest?

� Asynchronous technique deservesmore investigation.

� Is ventilation adequate with SI car-diac compressions?

� How should we limit interruptionsin compressions to assess effi-cacy?

Oxygen Delivery During CPR(Neonatal)—Intervention (NRP 738)

In neonates receiving cardiac com-pressions (P), does 100% O2 as theventilation gas (I), compared withlower concentrations of oxygen (C),increase survival rates, improve neu-rologic outcomes, decrease time toROSC, or decrease oxidative injury (O)?

Introduction

Neonatal resuscitation has historicallyfocused on achieving adequate oxy-genation as quickly as possible. Re-cently, it has been recognized thatexcessive oxygen administration can betoxic. Current guidelines recommend

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starting resuscitationwith low inspiredoxygen and then increasing inspiredoxygen as necessary as guided by pulseoximetry. However, once the re-suscitation has reached the need forchest compressions, it has been sug-gested to increase the Fio2. This PICOquestion is intended to consider evi-dence to determine if this is the corrector incorrect practice.


For the critical outcome of ROSC, wefound 8 animal studies (lambs/pigs/rats)216–223 all demonstrating no ad-vantage to 100% over 21% during CPR(very-low-quality evidence, downgradedfor bias and indirectness).

For the critical outcome of survival, wefound 8 of 9 animal studies (lambs/pigs/rats) reporting on survival dem-onstrated no advantage to 100% over21% during CPR.216–223 However, 1study (mouse) of 9 studies evaluatingthis outcome found an advantage to100% O2

224 (very-low-quality evidence,downgraded for potential bias, in-consistency, and indirectness). Allstudies combined showed 80/100(80%) versus 74/102 (73%) survivalfor 100% O2 versus air (not different).Eight studies with no advantageshowed 70/77 (91%) versus 71/79(90%) survival. One study with advan-tage for 100% showed 10/23 (43%)versus 3/23 (13%) survival (P50.02).

For the critical outcome of neurologicoutcome, we found 4 animal studies(pigs/rats/mice),218,221,222,224 reportingon neurologic outcome with varyingresults (very-low-quality evidence,downgraded for potential bias, in-consistency, indirectness, and im-precision). One demonstrated nodifference in neurologic deficits at 72hours, and ischemic neurons in hip-pocampal were not different.218 Onedemonstrated worse 4-hour neuro-logic examination in the 100% O2group.221 One demonstrated more

hippocampal apoptosis in the 100% O2group.222 One demonstrated morerapid restoration of cerebral bloodflow but no difference in histologicbrain injury scores.224

For the critical outcome of oxidativeinjury, we found 10 animal studiesreported on oxidative injury withvarying results212,213,216,219–223,225–227

(very-low-quality evidence, down-graded for potential bias, in-consistency, and indirectness). Sixstudies (pigs/mice) demonstrated nodifference in various oxidative injurymarkers,212,213,219–221,224 3 (lambs/rats) demonstrated more oxidativedamage from using 100% O2 includingapoptosis,216,222,226 and a pig studyreported less striatal and hippocampalapoptosis with 100% O2 compared with21% O2.

227


There are no human data to inform thisquestion.

Despite animal evidence showing noadvantage to the use of 100%oxygen, bythe time resuscitation of a newbornbaby has reached the stage of chestcompressions, the steps of trying toachieve ROSC using effective ventilationwith low-concentration oxygen shouldhave been attempted. Thus, it wouldseem prudent to try increasing thesupplementary oxygen concentration(Good Practice Guidance).

If used, supplementary oxygen shouldbeweanedas soonas theheart ratehasrecovered (weak recommendation,very-low-quality evidence).


Although most of the available animalevidence suggests that resuscitationusing air during neonatal chest com-pressions is feasible and that 100% O2as the resuscitation gas may increaseoxidative injury, we remain concernedthat we have no human data to prove

feasibility and none of the animalstudies have evaluated use of room-airCPR for more than brief asystole. Wevalue balancing the desire to preventongoing hypoxic injury in these pro-foundly asphyxiated neonates with thedesire to prevent subsequent hyper-oxic injury.

This was a much-debated topic. In thecase of hypotension and bradycardia,the experimental evidence is clear: Youonly need to use room air. Thus, in thiscase, we are making the recommen-dation independent of the evidence.Perhaps, we say, “Despite no evidence,for the following reasons, we recom-mend….” In training scenarios, oncechest compressions are started, failingto turn up O2 is a common error of thelearner. But is it a serious error? Theindirectness does not inform the rec-ommendation. We are not even follow-ing low-level animal evidence. We aremaking a conscious decision to take nonotice of the evidence. Can we say whythis group values giving oxygen forasystole? The task force considered theoption of making a neutral recom-mendation (with either 21% or 100%O2)and allowing councils to decide whatto do. Is this a place where we do notwant to suggest air or oxygen? Wehave no data, but we need to saysomething.

Knowledge Gaps

� Specific research is required, ie,studies in good transitional animalmodel of asphyxia-induced severebradycardia or asystole and anyneonatal human data.

ASSIST VENTILATION DEVICES ANDCPR FEEDBACK DEVICES

There are numerous techniques usedand advocated to ventilate effectively. Inaddition there are devices used to as-sess respiratory function and to pro-vide feedback during CPR. The following


reviews were undertaken to assess therole of alternative techniques to venti-late effectively when intubation is notfeasible or unsuccessful and to ascer-tain theevidenceof feedbackdevicesonresuscitation skill performance andoutcomes.

Laryngeal Mask Airway—Intervention (NRP 618)

In newborn infants at near term(greater than 34 weeks) or term whohave indications for intermittent posi-tive pressure for resuscitation (P), doesuse of a laryngeal mask as a primary orsecondary device (I), compared withmask ventilation or endotracheal in-tubation (C), improve response to re-suscitation or change outcome (O),including indicators of neonatal braininjury, achieving stable vital signs, in-creasing Apgar scores, long-term out-comes, reducing theneed forsubsequentintubation, or neonatal morbidity andmortality?

Introduction

Endotracheal intubation is the mostdifficult skill to learn and teach inneonatal resuscitation. The laryngealmask has recently been suggested asan alternative, either as a primary de-vice, replacing face-mask ventilation, oras a secondary device for failed or not-possible endotracheal intubation. ThisPICO question is intended to review theevidence for the utility and efficacy ofthe laryngeal mask for neonatal re-suscitation.


For comparison of laryngeal maskairway to face mask as a primarydevice (ie, use of laryngeal mask ven-tilation rather than bag-mask ventila-tion for infants at term requiring PPVfor resuscitation) we identified 3 ran-domized controlled trials enrollinga total of 469 patients:

� For the critical outcome of achiev-ing vital signs, we identified low-

quality evidence (downgraded forvery serious risk of bias) from 2small randomized clinical trialsand 1 large quasi-randomized clin-ical trial228–230 showing that thelaryngeal mask was more effectivethan the face mask (OR, 11.43; 95%CI, 4.01–32.58).

� For the critical outcome of needfor subsequent endotracheal in-tubation after failed laryngealmask or face mask, we identifiedlow-quality evidence (downgradedfor very serious risk of bias) fromthe same randomized clinical tri-als228–230 showing that the laryn-geal mask was more effectivethan the face mask (OR, 0.13; 95%CI, 0.05–0.34).

� For the critical outcome of in-creasing Apgar Score, we haveidentified low-quality evidence fromthe same randomized controlledtrials (downgraded for very seri-ous risk of bias); the method ofreporting precluded analysis ofthis outcome.

� We did not identify any evidence toaddress the critical outcomes ofindicators of brain injury orlong-term outcomes.

� For the important outcome ofmorbidity (gastric distention orvomiting), we identified low-quality evidence (downgraded forimprecision and very serious riskof bias) from the same randomizedclinical trials228–230 showing no dif-ference for any variable betweenthe laryngeal mask and the facemask (OR, 5.76; 95% CI, 0.7–47.32).

For comparison of laryngeal mask toendotracheal tube as a secondarydevice (ie, laryngeal mask or in-tubation when bag-mask ventilationhas failed) for infants at term requiringPPV for resuscitation, we identified thefollowing evidence (1 randomized clin-ical trial with 40 patients)231:

� For the critical outcome of achiev-ing vital signs or successful re-suscitation, we identified very-low-quality evidence (downgraded forimprecision, risk of bias) from 1randomized clinical trial231 showingthat laryngeal mask airway was aseffective as the endotracheal tube.

� For the critical outcome of needfor subsequent endotracheal in-tubation after failed bag-maskventilation, we identified very-low-quality evidence (downgraded forimprecision, risk of bias) fromthe same randomized clinical tri-al231 showing that the laryngealmask was as effective as the endo-tracheal tube.

� For the critical outcome of in-creasing Apgar score, we iden-tified very-low-quality evidence(downgraded for imprecision andrisk of bias) from the same random-ized clinical trial231; the method ofreporting precluded analysis of thisoutcome.

� For the critical outcome of mortal-ity, we identified very-low-qualityevidence (downgraded for impreci-sion and risk of bias) from thesame randomized clinical trial231

showing no difference betweenthe laryngeal mask or the endotra-cheal tube.

� We did not identify any evidence toaddress the critical outcome of indi-cators of brain injury or long-termneurologic outcomes comparinglaryngeal mask airway or endotra-cheal tube as a secondary device.

� For the important outcome ofmorbidity, we identified very-low-quality evidence (downgraded forimprecision and risk of bias) fromthe same randomized clinical tri-al231 showing more trauma to tis-sue when comparing laryngealmask versus endotracheal tube(OR, 2.43; 95% CI, 0.51–11.51).

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We suggest the laryngeal mask maybe used as an alternative to trachealintubation during resuscitation ofthe late-preterm and term newborn(more than 34 weeks) if ventilationvia the face mask is unsuccessful(weak recommendation, low-qualityevidence).

In the unusual situation where in-tubation is not feasible after failed PPV,the laryngealmask is recommended forresuscitation of the late-preterm andterm newborn (more than 34 weeks)(strong recommendation, good clinicalpractice).


In making these recommendations, weplace a moderate value in the provensafety and feasibility for a laryngealmask to provide ventilation in new-borns while recognizing the necessityfor more studies in other clinical set-tings (eg, premature infant). We alsoplace high value on the idea that analternative airway is a potentially life-saving intervention when face-maskventilation has failed and/or endotra-cheal intubation is unsuccessful or notfeasible. There is now reasonable evi-dence to add a recommendation for thelate-preterm infant.

Knowledge Gaps

� The effectiveness and safety of la-ryngeal mask airway comparedwith mask ventilation as the pri-mary interface in term and preterminfants; insertion technique, whichmodel, and how to teach its use

Newborn Infants Who Receive PPVfor Resuscitation, and Use ofa Device to Assess RespiratoryFunction—Diagnostic (NRP 806)

In newborn infants who receive PPV forresuscitation (P), doesuseof adevice toassess respiratory function with or

without pressure monitoring (I), com-pared with no device (C), change sur-vival to hospital discharge with goodneurologic outcome, IVH, time to heartrate greater than 100/min, broncho-pulmonarydysplasia, pneumothorax (O)?

Introduction

Resuscitation of babies at birth ofteninvolves assisting ventilation withpositive-pressure devices. Currentguidelines for this technique have al-ways involved recommending a specificpressure range to inflate the lungs.Recent research has indicated thatexcessive pressure can seriously injurethe lungs, particularly in babies bornpreterm, and somehave advocated thatresuscitation guidelines should bebased on volume rather than pressure.It has also been suggested thatmeasuring exhaled CO2 might indicateadequate ventilation. Devices for mea-suring both of these variables havebeen developed. This PICO question ismeant to assess the advisability ofrecommending their use during re-suscitation.


Flow and Volume Monitoring

For the critical outcome of survival tohospital discharge and IVH, we iden-tified low-quality evidence (downgradedfor risk of bias and imprecision) from 1pilot randomized controlled trial en-rolling 49 babies showing no bene-fit.232

For the critical outcome of time toheart rate greater than 100/min andneurologically intact survival, wefound no evidence.

For the important outcome ofbronchopulmonary dysplasia andpneumothorax, we found no evidence.

Capnography

For the critical outcome of survival tohospital discharge and IVH, weidentified low-quality evidence (down-

graded for risk of bias and impreci-sion) from 1 pilot randomized clinicaltrial enrolling 48 babies showing noevidence.233

For the critical outcome of time toheart rate greater than 100/minand neurologically intact survival,we found no evidence.

For the important outcome ofbronchopulmonary dysplasia andpneumothorax, we identified low-quality evidence (downgraded for riskof bias and imprecision) from 1 pilotrandomized clinical trial enrolling 48babies showing no evidence.233


Although a feasible technique, wesuggest against the routine use offlow and volume monitoring forbabies who receive PPV at birth, untilmore evidence becomes available(weak recommendation, low-qualityevidence).

Although a feasible technique, wesuggest against the routine use ofcapnography for babies who receivePPV at birth, until more evidencebecomes available (weak recommen-dation, low-quality evidence).


Weshould consider revising futurePICOquestions to embracenew technologiesfor more reasonable outcomes andbenchmarks rather than death anddisability. It was stressed that it is im-portant to point out the human factorspiece of the equation. The devices areonly as useful as how well the humancare provider can interface with andincorporate them appropriately intocare. Another point raised is that wehave process outcomes, but do theyimpact actual performance? Do weneed this to be a more stepwise ap-proach? What other process outcomesshould be included? In the future, weneed to look at device design, types of



alarms (visual or audio, color, font, etc).If this were a medication, we wouldsuggest against something with suchresource implications.

Knowledge Gaps

� There is a need for large studiespowered for important clinical out-comes to determine the role offlow and volume monitoring andcapnography in improving re-sponse to and outcomes of new-born resuscitation.

� There is a need for further re-search to determine whether rou-tine use of flow and volumemonitoring for task training innewborn resuscitation improvestraining or clinical outcomes.

� There is a need for specific re-search to determine whether con-tinuous monitoring of flow andvolume or exhaled CO2 levels com-pete with other essential auditoryand visual cues that need to beappreciated and responded to byresuscitation teams.

Use of Feedback CPR Devices forNeonatal Cardiac Arrest—Diagnostic (NRP 862)

In asystolic/bradycardic neonates re-ceiving cardiac compressions (P), doestheuseof feedbackdevicessuchasend-tidal carbon dioxide (ETCO2) monitors,pulse oximeters, or automated com-pression feedback devices (I), com-pared with clinical assessments ofcompression efficacy (C), decreasehands-off time, decrease time to ROSC,improve perfusion, increase survivalrates, or improve neurologic outcomes(O)?

Introduction

The current measure for determiningsuccessful progress in neonatal re-suscitation is to assess the heart rateresponse. Other devices such as CO2monitoring and pulse oximetry have

been suggested as more sensitivemeasures. This PICO question isdesigned to determine the current ev-idence regarding this issue.


For the critical outcomes of improvedperfusion, decreased time to ROSC,decreased hands-off time, in-creased survival rates, or improvedneurologic outcomes, we found nospecific data.

Increased exhaled CO2: Five smallobservational studies (2 piglet post-transitioned models,234,235 2 dog post-transitioned models236,237 (these latter2 articles were the identical sampleof dogs and data but published inseparate journals), and 1 humanstudy238 of very low quality (down-graded for indirectness and risk ofbias) assessed the ETCO2 levels as-sociated with the onset or presence/absence of ROSC.

� One piglet study234 and the dogstudies236,237 associated the pres-ence of decreased time to ROSCwith an ETCO2 of 27 to 28 mm Hg.CPR in these studies was startedafter 5 to 10 minutes of cardiacarrest.

� One piglet study235 associated thepresence of a heart rate greaterthan 60/min with an ETCO2 of 14 mmHg (sensitivity, 93%; specificity,81%). CPR was started at onsetof asystole.

� One human study covered a wideage range of children, 1 week to10 years.238 The majority wereout-of-hospital arrests. ETCO2 levelsin all patients who did not attainROSC never rose above 15 mm Hg.


In asystolic/bradycardic neonates,we suggest against the routine re-liance on any single feedback devicesuch as ETCO2 monitors or pulseoximeters for detection of ROSC until

more evidence becomes available(weak recommendation, very-low-qualityevidence).


Several questions were raised: Shoulddetection of ROSC be the only realoutcome for the question becauseidentifying this is the first step to re-covery? Thus, it is a critical tool fordetermining if youractionsareeffectiveor if you need to consider other inter-ventions. Was there a need to rate theeffectiveness of the equipment as thecritical outcome, or is the effect on thepatient what is important? Does thedevice measure what it is supposed tomeasure? What about human factorsissues? Can providers effectively usethe equipment? Does it impact out-come?

Knowledge Gaps

� There is a need for large studiespowered for important clinical out-comes to determine the role offlow and volume monitoring andcapnography in improving re-sponse to and outcomes of new-born resuscitation.

� There is a need for further re-search to determine whether rou-tine use of flow and volumemonitoring for task training innewborn resuscitation improvestraining or clinical outcomes.

� There is a need for specific re-search to determine whether con-tinuous monitoring of flow andvolume or exhaled CO2 levels com-pete with other essential auditoryand visual cues that need to beappreciated and responded to byresuscitation teams.

POSTRESUSCITATION MANAGEMENT

ILCOR previously reviewed postre-suscitation strategies that focused on

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glucosecontroland the implementationof therapeutic hypothermia tominimizeor avoid reperfusion injury fromintrapartum hypoxia-ischemia in well-resourced settings. For this cycle, weonly reviewed the potential role oftherapeutichypothermia tominimizeoravoid reperfusion injury from intra-partum hypoxia-ischemia where resour-ces are limited.

Limited-Resource–InducedHypothermia—Intervention (NRP734)

In term infants with moderate/severehypoxic-ischemic encephalopathy man-aged in resource-limited countries (P),does therapeutic hypothermia to coretemperature of approximately 33.5°Cfor 72 hours delivered by passive hy-pothermia and/or ice packs (I), versusstandard therapy (C), improve therates of death, neurodevelopmentalimpairments at 18 months to 2 years(O)?

Introduction

Therapeutic hypothermia has beenshown to reduce mortality and mor-bidity in term and near-term newbornswho have had a hypoxic-ischemic insultand are at risk for evolving encepha-lopathy. This therapy has generallybeen restricted to developed countrieswhere resources and regional systemspermit the therapy to be administeredunder a strict protocol. This PICOquestion is intended to determine iftherapeutic hypothermia can practi-cally and effectively be practiced incountries with limited resources.


For the critical outcome of death ordisability, we identified very-low-qualityevidence (downgraded for risk of biasand indirectness) from 2 randomizedcontrolled trials239,240 enrolling 338 in-fants showing benefit to the use oftherapeutic hypothermia (OR, 0.43; 95%CI, 0.26–0.7).

For the critical outcome of death tolatest follow-up, we identified very-low-quality evidence (downgraded forrisk of bias, inconsistency, and in-directness) from 4 randomized con-trolled trials239–242 enrolling 416 infantsshowing no benefit to the use of thera-peutic hypothermia (OR, 0.72; 95% CI,0.44–1.16).


We suggest that newly born infantsat term or near-term with evolvingmoderate-to-severe hypoxic-ischemicencephalopathy in low-income coun-tries and/or other settings with limitedresources may be treated with thera-peutic hypothermia (weak recommen-dation, low-quality evidence).

Cooling should only be considered,initiated, and conducted under clearlydefined protocols with treatment inneonatal care facilities with the capa-bilities for multidisciplinary care andavailability of adequate resources tooffer intravenous therapy, respiratorysupport, pulse oximetry, antibiotics,anticonvulsants, and pathology testing.Treatment should be consistent withthe protocols used in the randomizedclinical trials in developed countries, ie,cooling to commence within 6 hours,strict temperature control at 33°C to34°C for 72 hours and rewarming overat least 4 hours.


In making this recommendation, weplace a higher value on the demon-strated effectiveness of simple coolingmethods and the lack of harm associ-ated with these methods over thepaucityof evidencespecific toresource-limited settings.

It is difficult to define a low-resourcesetting. Even within a country (eg, In-dia) resources may vary widely. Simplemethods of cooling are successful inlowering body temperature. There was

a concern that passive cooling maynot be so harmless (eg, extreme hy-pothermia, inappropriate hypother-mia). Low-resource areas do not havenursing care to monitor the babiesclosely.

Knowledge Gaps

� Further adequately powered ran-domized controlled trials of simplemethods of cooling in resource-limited settings are required to im-prove the quality of evidence relatingto this question.

� Specific regional guidelines shouldtake account of public health systempriorities for allocation of availableresources and the availability of suf-ficient nursing and ancillary resour-ces to safely and effectively delivercooling therapy in the facility.

DISCONTINUING RESUSCITATION

Deciding how long resuscitative effortsshould continue in a newly born infantwith no heart rate and/or absent res-pirations with a very low heart rateafter sustained resuscitative effortsremains a critically important and dif-ficult management decision. In recentyears, long-term outcomes have shownsome improvement.

Delivery Room Assessment for LessThan 25 Weeks and PrognosticScore (NRP 805)

In extremely preterm infants (less than25 weeks) (P), does delivery room as-sessment with a prognostic score (I),compared with gestational age as-sessment alone (C), change survival to18 to 22 months (O)?

Introduction

Antenatal assignment of prognosis forsurvival and/or disability of the neonateborn extremely preterm has gener-ally been made on the basis of ges-tational age alone. Recently, scoringsystemsforincludingadditionalvariables





suchasgender,useofmaternalantenatalsteroids, and multiplicity have been de-velopedinaneffort to improveprognosticaccuracy. This PICO question was de-veloped to examine the utility of thesesystems.


There is no evidence that addresses theclinical prospective use of prognosticscoring (the use of composite survivaldata using gestational age and otherparameters) in infants of less than 25weeks of estimated gestational age.

There is increasing retrospective evi-dence that prognostic accuracy is im-proved by using additional informationsuch as birth weight, appropriatenessof weight for gestational age, use ofmaternal antenatal steroids, multiplic-ity, and gender243–247 (low-quality evi-dence), but there are no prospectivestudies showing the postnatal effect ofsuch improved accuracy in predictingoutcome.


There is insufficient evidence to sup-port theprospectiveuseof anydeliveryroom prognostic score presently de-scribedoverestimatedgestational ageassessmentalone inpreterm infantsofless than 25 weeks of gestation. Noscore has been shown to improve theability to estimate the likelihood ofsurvival through either 30 days or inthe first 18 to 22 months after birth.

In individual cases, when constructinga prognosis for survival at gestationsbelow 25 weeks, it is reasonable toconsider variables including perceivedaccuracy of gestational age assign-ment, the presence or absence ofchorioamnionitis, and the level of careavailable for location of delivery. It isalso recognized that decisions aboutappropriatenessof resuscitation below25weeks of gestation will be influencedby region-specific guidelines establishedby regional resuscitation councils.


In making this statement, we puta higher value on the lack of evidencefor a generalizable prospective ap-proach changing important outcomesover improved retrospective accuracyand locally validated counseling poli-cies. For antenatal counseling, themostuseful data would give outcome figuresfor babies alive at the onset of labor, notjust those born alive or admitted to theneonatal intensive care unit. In reality,many are already using such extendeddata in antenatal counseling to try toprovide parents and healthcare pro-fessionals with the most accurate esti-mates for mortality (and morbidity).

It would obviously be preferable if therewere studies to show that using suchdata can prospectively improve theoutcomefor thesebabies:Doesusingthemost accurate information have a posi-tive influence on the difficult decisionsmade about whether intensive careshould be implemented?

There was agreement to amend thetreatment recommendation to includeconsideration of possible inaccuracy ofgestational age assessment, as well as toinclude evaluation for chorioamnionitis,and level of subsequent care that may beavailable. A question was raised with re-gard to the fact that we included weightsin previous statements about prognosis;however, those were taken out to allowcouncils to make independent recom-mendations. Should antenatal steroids bementioned in the treatment recommen-dation? The listmaybecomeexhaustiveasmore factors are added (eg, gender).

Knowledge Gaps

� Insufficient or absent data con-cerning timing of death, ie, earlyversus later death

� Lack of information on factors otherthan gestational age known beforebirth

� Limited information on use ofcombined antenatal and postnatalinformation

� Inability to fully distinguish be-tween outcomes driven by practice(eg, belief that mortality is univer-sal below a certain gestational age),surrogate decision making by parents,and physiologic limitations

Apgar Score of 0 for 10 Minutes orLonger—Prognosis (NRP 896)

In infants with a gestational age of 36weeks or greater and an Apgar score of0 for 10 minutes or longer, despite on-goingresuscitation(P),what is therateofsurvival to NICU admission and deathor neurocognitive impairment at 18 to22 months (O)?

Introduction

There has been an ongoing controversyas to how long after one has beenattempting resuscitation after birth, anda heart rate cannot be detected, shouldonecontinueordiscontinueresuscitationefforts. The balance must be betweenceasing too early, when ROSC and long-term survival may still be achievable,and continuing too long, when ROSC mayoccur, but earlydeathoranunacceptabledegree of neurologic injury may haveoccurred. The Apgar score of 0 hasclassically been the criterion, because itindicates no detectable signs of life. Therecommended duration of resuscitativeefforts after birth has variously been 15,andmorerecently10minutes, afterbirth.

The controversy has been generatedfrom the following uncertainties: (1) Itis often not clear whether resuscitationefforts have taken place throughoutthe 10-minute period, (2) Theremay bequestions about whether the scorehas indeed been 0 throughout the 10minutesandnot just at 10minutes, and(3) Have resuscitation efforts beenoptimal throughout the 10 minutes?Recently, the 10-minute guideline hasbeen subjected to further controversy,

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with published reports from thera-peutic hypothermia trials of an in-creasing number of intact survivorsafter 10minutes of an Apgar score of 0.


For the critical outcome of death up to22 months, very-low-quality evidence(downgraded for risk of bias, inconsis-tency, and imprecision) from 6 studiesencompassing 8 case series showedthat 75 of 129 infants (58%) with an es-timated gestational age of 36 weeks orgreater and an Apgar score of 0 at 10minutes of life died before 22 months ofage.248–253 Results from 3 of these stud-ies performed after 2009 that includednested observational series of casesfrom 3 randomized clinical trials oftherapeutic hypothermia and a series ofinfants who received therapeutic hypo-thermia outside a randomized trial (low-quality evidence, downgraded for risk ofbias) found that 46 of 90 infants (51%)with an Apgar score of 0 at 10 minutesdied before 22 months of age.250,251,253

For the critical outcome of death ormoderate/severe neurodevelopmentalimpairment at 22 months of age orolder, 6 studies (very-low-quality evi-dence, downgraded for risk of bias,inconsistency, indirectness, and impre-cision) showed this outcome in 106 of129 infants (85%) with a gestational ageof 36 weeks or greater and an Apgarscore of 0 at 10 minutes of life.248–253

Results from 3 of these studies per-formed after 2009 (very-low-quality evi-dence, downgraded for risk of bias,inconsistency, indirectness, and impre-cision) that included nested observa-tional series in randomized clinical trialsof therapeutic hypothermia and seriesof infants who received therapeutic hy-pothermia showed that this adverseoutcome occurred in 68 of 90 infants(76%) with an Apgar score of 0 at 10minutes. Among the 44 survivors of thesestudies, 22 (50%) survived without major/moderate disabilities. Among the 56cooled infants in these studies, 15 (27%)

survived without major/moderate dis-abilities250,251,253 (very-low-quality ev-idence, downgraded for risk of bias).

No studies differentiated betweensevere and moderate disability.

None of the studies described theresuscitation procedures that wereprovided.


An Apgar score of 0 at 10 minutes is astrong predictor of mortality and mor-bidity in late-preterm and term infants.We suggest that, in babies with an Apgarscore of 0 after 10 minutes of resusci-tation, if the heart rate remains unde-tectable, it may be reasonable to stopresuscitation; however, the decision tocontinue or discontinue resuscitativeefforts should be individualized. Vari-ables to be considered may includewhether the resuscitation was con-sidered to be optimal, availability ofadvanced neonatal care, such as ther-apeutic hypothermia, specific circum-stances before delivery (eg, knowntiming of the insult), and wishes ex-pressed by the family (weak recom-mendation, very-low-quality evidence).


In making this statement in infants of35 weeks or greater with an Apgarscore of 0 for 10 minutes or longer, thelikelihood of dying or having severeormoderate developmental disabilitiesat 18 to 24 months is very high. Studiesthat included 69 infants with an Apgarscore of 0 at 10 minutes after birth whowere successfully resuscitated andrandomly assigned to hypothermia ornormothermia, and case series of 21additional infants who were managedwith therapeutic hypothermia, suggestimprovement in outcomecomparedwithpreviously reported cohorts. Amongthese 90 infants, 45 (50%) died and 22(24%) survived without major or mod-erate disability at 18 to 24 months.

However, the number of infants with noheart rate at 10 minutes who died in thedelivery room is unknown.

This topic resulted in a long and spir-ited debate. A question was raised as tohowcanwesay thatweshould considerstopping with a 24% possibility of sur-vival without major handicap? Is 10minutes sufficient time to make thisdecision? It was suggested not to usethe word adequate, because the re-suscitation was not assessed. Whatwould the adults do with 20% chance ofsurvival? However, it was pointed outthat it is not a 20% chance, because notall babies got to cooling. Someone ad-vocated using the term discontinue in-stead of withdraw. The term adequatecaused a lot of debate. What do wemeanby it? Can it be clearer? Concern wasexpressed that providers will likely notuse science to guide the decisions forthis situation and will likely use theirown judgment. Parents tend to choosecontinuation even when the data arepresented to them. The decision to con-tinue or discontinue should be based onconsultation with the family. The optimalway to restore circulation can be in thequalifier. An Apgar score of 0 at 10minutes is a strong predictor of dis-ability at all gestations.

Knowledge Gaps

Themajorflaw in theavailable scientificevidence regarding outcome of termneonateswith asystole after 10minutesof adequate resuscitation is the ab-sence of data regarding

� Number of infants born in the studycenters or the transferring centerswith asystole at 10 minutes whowere not actively resuscitated (inthe hypothermia studies many weretransfers)

� Number of infants born in the studyor the transferring centers with asys-tole at 10 minutes in whom deliveryroom resuscitation was attemptedand unsuccessful


� Data regarding the quality and exten-sion of resuscitation of these infants

� Only a prospective international reg-istry with all needed information ofinfants with asystole/heart rate lessthan 60/min after 10 minutes of ad-equate resuscitation may provide ev-idence of sufficient scientific merit toanswer this prognostic question

Predicting Death or Disability ofNewborns of Greater Than 34Weeks Based on Apgar and/orAbsence of Breathing—Prognosis(NRP 860)

In newborn infants of greater than 34weeks of gestation, receiving PPV atbirth in settings where resources arelimited (P), does presence of heart ratewith no spontaneous breathing orApgar scores of 1 to 3 at greater than5 minutes predict mortality or mor-bidity or cerebral palsy (O)?

Introduction

The Apgar score is intended to bea retrospective predictor of outcome,particularly at 5 minutes of age. It hasbeen suggested that an Apgar score of0 at 10minutes of age is an indication toconsider discontinuing resuscitationefforts (see NRP 896), but there havebeen no other levels of Apgar assess-ment by which one might make dis-continuation decisions, such as Apgarscore of 3 or less at 20 minutes. ThisPICO question is intended to review therecent evidence regarding these addi-tional predictors.


Apgar Score at 20 Minutes

For all the outcomes, we could not findstudies that reported on individual Apgarscores (1, 2, or 3) beyond 10minutes. Onevery-low-quality study (downgraded forindirectness)reportedonApgarscoresat20 minutes but included patients with anApgar score of 0.254 This study reported

that inbabiesweighinggreater than2500gwith an Apgar score of 0 to 3 at 20minutes, themortality was 59%, and 57%of survivors developed cerebral palsy.

Apgar Score at 10 Minutes

For the critical outcome of death, weidentified low-quality evidence (down-graded for imprecision) from 2 ran-domized studies involving babies whoparticipated in induced-hypothermiastudies.251,255 One study251 reportedmortality of 64%, 47%, and 39% for Apgarscore of 1, 2, and 3, respectively, with anOR of 1.42 (95% CI, 1.19–1.69) at 18 to22 months. The other study255 reportedoutcomes from the same study, but at 6to 7 years. Babies with Apgar scores of 1,2, and 3 had mortality rates of 67%, 43%,and 27%, respectively, if they were man-agedwith induced hypothermia and 63%,57%, and 62% if they were not cooled.

For the critical outcomeofmoderate/severe disability, we identified low-quality evidence (downgraded for im-precision) from 2 randomized studiesinvolving babies who participated in in-duced hypothermia studies,251,255 one251

reporting the outcome in 50%, 63%, and38% for Apgar scores of 1, 2, and 3, re-spectively, with an OR of 1.30 (95% CI,1.06–1.58) at 18 to 22 months. The otherstudy255 reported at 6 to 7 years of lifethat 100%, 75%, and 9% of babies withApgar score of 1, 2, and 3, respectively,had moderate/severe disability if man-aged with induced hypothermia and67%, 67%, and 71% if not managed withhypothermia, although the sample sizewas small.

No Spontaneous Respiration

For the critical outcome of death,we identified very-low-quality evidence(downgraded for imprecision) from 2observational studies256,257 that time tospontaneous respiration of more than30 minutes was associated with 52% to77% mortality.

For the critical outcome of cere-bral palsy or abnormal neurologic

findings, we identified very-low-qualityevidence (downgraded for impreci-sion)256–258 that time to respiration ofmore than 30 minutes was associatedwith 35% cerebral palsy and 67% to100% abnormal neurologic findings.

For the critical outcome of deathand/or moderate-to-severe disabil-ity, we identified very-low-quality evi-dence (downgraded for imprecision)from 2 observational studies259,260 thattime to spontaneous respiration of 10 to19 minutes and more than 20 minuteswas associatedwith this outcome in 56%and 88% of patients, respectively,259 andtime to spontaneous breathing of 30minutes or more was a predictor of thisoutcome (OR, 2.33; 95% CI, 1.27–4.27).


Absence of spontaneous breathing oran Apgar score of 1 to 3 at 20minutes ofage in babies of greater than 34 weeksof gestation but with a detectable heartrate are strong predictors of mortalityorsignificantmorbidity. Insettingswhereresources are limited, we suggest that itmay be reasonable to stop assistedventilation inbabieswithnospontaneousbreathing despite presence of heart rateor Apgar score of 1 to 3 at 20 minutes ormore (weak recommendation, very-low-quality evidence).


In making this statement, in infants ofgreater than 34 weeks with an Apgarscore of 0, 1, 2, or 3 for 20 minutes ormore, the likelihood of dying or havingsevere or moderate developmental dis-abilities at 18 to 24 months is very high.Importantly, eachof thestudies reviewedwas conducted in a resource settingwhere therapeutic hypothermia waslikely to be available (see NRP 734).

Perhaps there is a publication biaswhen those babieswho did not respondat 20 minutes are not included in thenumbers. The question was raised, if

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the prognosis is the same, why wouldwe recommend something differentfor resource-limited settings? A re-sponse was that in resource-limitedregions, there will likely not be theregional systems and postresusci-tationneonatal intensive care facilitiesand subspecialty personnel that wereavailable in the recent studies re-viewed in the Consensus on Science.If such facilities are available, thistreatment recommendation may beless applicable.

Knowledge Gaps

� No studies identified from low-resource settings

� Outcome of babies with delayedonset of breathing who are man-aged with induced hypothermia inlow-resource settings.

� Outcome of babies with gasping orirregular breathing and a heart ac-tivity at 20 minutes of life

EDUCATIONAL TECHNIQUES FORTEACHING, ASSESSING, ANDMAINTAINING RESUSCITATIONKNOWLEDGE AND SKILLS

Resuscitation Training Frequency(NRP 859)

For course participants including (a)trainees and (b) practitioners (P), doesfrequent training (I), compared with lessfrequent training (annual or biennial) (C),change all levels of education or prac-tice, prevention of adverse outcomes,overallmortality, scenarioperformance,medical knowledge, psychomotor per-formance, provider confidence, coursesatisfaction (O)?

Introduction

Training in the cognitive, technical, andbehavioral skills necessary for successfulneonatal resuscitation has historicallybeen conducted at varying intervals oftime,andthereis littleevidencetosupportthe use of one interval overanother. As an

example, the national steering commit-tee of the US Neonatal Resuscitation Pro-gram has recommended that traineescomplete theprogramonceevery2 years,but in the United Kingdom, 4 years is therecommended interval; there is no ob-jective evidence to validate these inter-vals. It is intuitive that individual traineeswill require different training intervalsto facilitate optimal acquisition and main-tenance of different skills. This PICOquestion is intended to update the evi-dence as to what may be the most ef-fective strategy.


Sixteen studies were identified that haveinvestigated this PICO question. Ten ran-domized controlled studies261–270 and 6nonrandomized controlled trials271–276

were identified for inclusion.

Theevidenceforfrequencyofresuscitationtraining is very low quality (downgradedfor high risk of bias, inconsistency, andimprecision), with the exception of studiesofpsychomotorperformance,whichareofmoderate quality (downgraded for risk ofbias). Meta-analyses were greatly limitedby the heterogeneity between studies oftraining frequency, educational inter-ventions, and outcomes.

For the critical outcome of patientoutcomes, 2 studies271,275 of very lowquality (downgraded for high risk ofbias, inconsistency, and imprecision)looked at endotracheal intubation suc-cess. Both studies included psychomo-tor skill training on an airway simulator,and Nishisaki275 included simulation-based training. There was no signifi-cant difference in first-time intubationsuccess (RR, 0.879; 95% CI, 0.58–1.33) orany intubation success (RR, 0.87; 95% CI,0.65–1.17) between the providers whowere exposed to frequent training andcontrols.

For the important outcome of pre-vention of adverse events, the Nishi-saki study also included the importantoutcome of prevention of adverse out-

comes and airway injury as a second-ary outcome. No significant differencewas seen between groups (RR, 1.097;95% CI, 0.747–1.612).275

For the important outcome of perfor-mance in simulation, 3 studies264,267,273

of very low quality (downgraded for highrisk of bias, inconsistency, and impreci-sion) investigated the important outcomeof performance in simulated scenariosusing both validated and nonvalidatedevaluations. In all studies, subjects in theintervention groups trained more fre-quently than controls. The range of timebetween initial course completion andfirst additional training session was 1 to4 months. The educational interventionswere heterogeneous, including in-dependent and facilitated practice onairway simulators,264 didactic lectures,skill station practice, mock codes,273 andperiodic review of course material andcase-based study.267 Kovacs264 andStross267 found no significant differencebetween frequent and infrequent prac-tice with respect to simulation-basedperformance. Only 1 of these studies(Nadel273) offered quantitative data: Af-ter averaging of multiple outcomes,there was a trend to improved perfor-mance in those exposed to increasedfrequency of training compared withcontrols (RR, 1.51; 95% CI, 0.971–2.35).

For the important outcome of psy-chomotor performance, there were8 studies261,262,266,267,269,273,274,276 ofmoderate quality (downgraded for riskof bias) that evaluated the importantoutcome of impact of frequent trainingon psychomotor performance, demon-strated on a task trainer or simulator.With the exception of O’Donnell276

and Stross267 (which were neutral tothe question), studies demonstratedimprovements in psychomotor perfor-mance with no negative effect. Therange of time between course com-pletion and first additional trainingsession was 1 week to 6 months.The educational interventions were



again heterogeneous. Psychomotor tasktrainers were used to achieve compe-tency in a specific technical skill, in-cluding practice on a chest compressiontask trainer (Niles274), neonatal airwaymanagement task trainer (Ernst262), ora CPR task trainer where both chestcompressions and ventilation were em-phasized.261,266,276 The study by Stross267

included periodic review of course ma-terial and case-based study.267 The edu-cational intervention in the Nadel273

study used didactic lectures, skill stationpractice, and mock codes. Although 8studies were identified, only 1 random-ized273 and 2 observational studies267,276

with dichotomous quantitative data wereincluded in the analysis. The 1 random-ized study273 demonstrated a significantimprovement in psychomotor skills insubjects in the intervention group whencompared with controls. One randomizedstudy266 with multiple outcomes showedsignificantly improved performance ofthe important outcomes of manual ven-tilation volume and chest compressiondepth after practice every 3 months.However, an improvement in psychomo-tor skills in the intervention groups wasnot seen when 3 studies267,273,276 wereincluded in a meta-analysis after averag-ing of scores (RR, 1.38; 95% CI, 0.87–2.2).

For the important outcome of knowl-edge, 5 studies263,268,270,273,276 of verylow quality (downgraded for high risk ofbias, inconsistency, and imprecision)investigated the relationship betweenfrequent training and the importantoutcome of acquisition of medicalknowledge assessed by written tests ororal exams. Studies by Nadel,273 O’Don-nell,260 and Turner254 demonstratedsustained knowledge with refresherswhen compared with controls, whereasKaczorowski263 and Su252 were neutralto the question. The educational inter-ventions for these studies have beendescribed previously except for 2 stud-ies: Su used a knowledge exam andmock resuscitation at 6months, and the

Kaczorowski263 study included subjects inthe intervention groups either watchinga newborn resuscitation education videoor hands-on practice. The range of timebetween course completion and firstadditional training session was 1 to 6months. Although 5 studies were identi-fied, only 2 had quantitative data.270,273

The analysis of the 2 observational stud-ies was not possible because it was dif-ficult to average the means 6 SDs andthen pool the 2 studies for a meta-analysis. The Nadel273 study found a sig-nificant improvement in knowledge withmore frequent training in a short answertest (mean scores 73611 versus 60610;P50.0003). The Turner254 study showedsignificant improvement in 2 out of 3 testscores in the intervention group (meanscores 7.1 versus 6.2 and29.0 versus 25.8,respectively; P,0.05 in both cases).O’Donnell260 demonstrated lower testscores in the control group than in theintervention group (P,0.04).

For the nonimportant outcome of pro-vider confidence, Montgomery265 foundthat subjects who practiced CPR for 6minutes every month were more likelythan controls to report that they feltconfident (RR, 1.60; 95% CI, 1.27–2.01),and Nadel273 found improved confidencein both leadership and technical skills.

No study demonstrated a negative ordetrimental effect frommore frequenttraining. Publication bias was difficultto assess.


We suggest that training should be re-current and considered more frequentlythanonceperyear.Thisretrainingmaybecomposed of specific tasks and/or be-havioral skills, depending on the needs ofthe trainees (weak recommendation,very-low-quality evidence).


In drawing our conclusions, we placevalue on improved psychomotor skills,

knowledge, and provider confidenceduring more-frequent training versusless-frequent training (and versus theestablished and unproven practice oftraining every 1 to 2 years).

The debate included the fact that thePICO question does not specify that it isresuscitation training, although thesearch did restrict itself to this. Shouldthe costs of training be addressed?However, it was noted that it was hard tocomment on cost based on studies,because the interventions themselveswere so different. Could the follow-upprograms be briefer and more fo-cused on needs? What is best for thepatient? What is the cost to the childand family when the patient does notreceive adequate resuscitation? Whatis a technical proficiency program?How do we achieve it? There is no as-sessment of translation of increasedtraining to improved outcomes. Weneed data to show that improved ed-ucation isworth the staff time. ThePICOquestion specifically avoided lookingat studies about decay of knowledgeand skills.

Knowledge Gaps

� Although some outcomes are ofcritical importance, the quality ofevidence is very low. Serious meth-odological flaws occur, such as lackof randomization, multiple primaryoutcomes with inadequate samplesize and power analysis, lack ofblinding, controls that consist of noeducational intervention resulting ina comparison of training to no train-ing, insufficiently validated evaluationtools, and significant heterogeneityof outcomes and interventions.

� There is a need for well-designedand well-powered clinical trials,possibly cluster randomized, thatanswer key questions with criticaloutcomes: How frequently shouldlearning occur? What type of inter-vention is most effective? What

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validated tools are available tomeasure educational outcomes?

� How do high-opportunity versus low-opportunity environments differ intheir need for frequent training?

� Did we take experience into ac-count?

� What about knowledge, skills,and behaviors?

� Are patient outcomes lacking?

� Is cost impact lacking?

� Is high-frequency, low-dose train-ing effective?

� Decay and boosting rates?

� Should we add “within the con-straints of local resources”?

� Reinforcement from otherdomains, for example

Neonatal Resuscitation Instructors(NRP 867)

In neonatal resuscitation instructors (P),does formal training on specific aspectsof how to facilitate learning (I), comparedwith generic or nonspecific training (C),change clinical outcome, improve alllevels of education or practice (O)?

Introduction

Around theworld,millionsofhealthcareprofessionals bear the responsibility forresuscitating neonates in the deliveryroom, and theymustnotonly acquire thenecessary cognitive, technical, and be-havioral skills but also maintain themover time, often fordecades. The preciseroles and mandatory skills of theinstructors charged with traininghealthcare professionals have yet to bedefined, and thus how to best prepareinstructors to fulfill these roles andacquire these skills is not yet objectivelydescribed. It is intuitive that training ofinstructors should be based on specificlearningobjectivestargeting thespecificinstructor skills that are necessary tofacilitate the acquisition of specific skillsin specific populations of learners.

Comprehensive assessment of resusci-tation instructor training requiresidentification and development of (1)objective markers of performance forinstructors, (2) appropriate objectivemarkersofperformancefor thetraineeswho are trained by the instructors, and(3)objectivemarkersofpatientoutcomethat are directly related to howwell theywere resuscitated. This PICO question isintended to identify literature that ispertinent to these and other issues in-volving the preparation of instructor ofneonatal resuscitation.


For the critical outcome of improve-ment in patient outcome, we identi-fied no evidence.

For the critical outcome of improve-ment in learner performance in thereal clinical environment, we identifiedvery-low-quality evidence from 1 ran-domized clinical trial277 (downgradedfor indirectness, risk of bias, and im-precision) that providing structuredself-reflection and peer group feed-back to psychiatry registrars improvedtheir students’ performance of stan-dardized psychiatric interviews.

For the critical outcome of improve-ment in learner performance ineducational settings, we identifiedvery-low-quality evidence (downgradedfor indirectness, imprecision, and riskof bias) from 1 randomized clinical tri-al278 in which 18 emergency medicineinstructors were randomly assigned to2 intervention groups and trained 193medical students. The study found thatlearners trained by instructors whounderwent a 2-day teacher trainingcourse focused on education principlesperformed at an equal or lower level ofproficiency in technical skills whencompared with those trained byinstructors who did not attend the 2-daycourse.

For the critical outcome of improve-ment in all levels of education or

practice, we identified low-quality ev-idence (downgraded for indirectnessand bias) from 5 randomized clinicaltrial278–282 enrolling 271 participants(not estimable). Several studies didnote at least temporary deteriorationin instructor performance after com-mencement of new instructor trainingintervention.

For the critical outcome of improve-ment in clinical outcome, we identi-fied no evidence.

For the important outcome of im-provement in instructor perfor-mance, we identified very-low-qualityevidence (downgraded for indirectnessand bias) from 5 randomized clinicaltrials278–282 and 2 nonrandomized tri-als.283,284 No meaningful numericalsummary of the results of these studiescould be performed. These studies in-dicate that preparation of instructorsproduces inconsistent results in termsof instructor performance. While it doesseem that written and verbal feedback,delivered in a constructive and timelymanner, often produces improvementin instructor performance, in otherinstances posttraining deterioration inaspects of instructor performance wasseen, at least initially.


We suggest that training of re-suscitation instructors incorporatetimely, objective, structured, in-dividually targeted verbal and/orwritten feedback (weak recommen-dation, low-quality evidence).


While common sense dictates thatinstructors be properly prepared be-fore engaging learners, it is clear thatsuch instruction must be based onspecific learning objectives targetingthe specific skills that are necessary tofacilitate learning. Definitions of theseskills will require collaboration with



colleagues in fields such as humanfactors and ergonomics who have ex-perience in examining human perfor-mance in high-risk domains (similar tothe delivery room) rather than relyingsolely on those with expertise in tra-ditional education settings such as theclassroom.

Deliberations of the Task Force andWriting Group

The PICO question may be too global/broad. Perhaps we need to be morespecific in the future. We may need tomove away from dependence on tra-ditional methodologies and look tothose industries where adults aretrained to beproficient in specific tasks.Instructors need to know how to dospecific tasks and give feedback toimproveperformance.Perhapswehavemade instructors poor trainers. Peoplewho develop curricula need to addressthis critical deficit. How do we teachtask proficiency? That is what is mostneeded.

Knowledge Gaps

� How is optimal instructor perfor-mance defined?

� What are the skills necessary toachieve this?

� What are the optimal methods forselection of candidate instructors,initial skill acquisition by instructors,ongoing maintenance of instructorskill, and (objective and subjective)assessment of instructor skill?

2010 PICO QUESTIONS NOTREVIEWED IN 2015

� Suctioning (other than meconium)

� Inflation pressures

� Face mask characteristics

� CO2 detectors to confirm endotra-cheal tube placement

� Epinephrine dose and route

� Volume expansion

� Sodium bicarbonate

� Glucose

� Therapeutic hypothermia

� Personnel needs at elective cesar-ean delivery

� Briefing and debriefings duringlearning activities

ACKNOWLEDGMENTSWe thank the following evidencereviewers (the Neonatal ResuscitationChapter Collaborators) for their great ef-fort, due diligence, and expertise withregard to the reviews contained in thissection: David W. Boyle, Steve Byrne, ChrisColby, Peter Davis, Hege L. Ersdal, MarilynB. Escobedo, Qi Feng, Maria Fernanda deAlmeida, Louis P. Halamek, TetsuyaIsayama, Vishal S. Kapadia, Henry C. Lee,Jane McGowan, Douglas D. McMillan,Susan Niermeyer, Colm P. F. O’Donnell,Yacov Rabi, Steven A. Ringer, Nalini Sin-ghal, Ben J. Stenson, Marya L. Strand,Takahiro Sugiura, Daniele Trevisanuto,Enrique Udaeta, GaryM.Weiner, and CheoL. Yeo. We also acknowledge the com-ments received during the public period.

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DISCLOSURES

2015 CoSTR Part 7: Neonatal Resuscitation: Writing Group Disclosures

Writing Group Member Employment ResearchGrant

Other ResearchSupport

Speakers’Bureau/Honoraria

ExpertWitness

OwnershipInterest

Consultant/AdvisoryBoard

Other

Jeffrey M. Perlman Weill Cornell MedicalCollege

None None None None None None None

Jonathan Wyllie James Cook UniversityHospital


Khalid Aziz University of AlbertaPediatrics


Ruth Guinsburg Federal University ofSao Paulo


John Kattwinkel University of VirginiaHealth System


Han-Suk Kim Seoul NationalUniversity College of

Medicine


Helen G. Liley Mater Mother’s Hospital NHMRC(Australia)*

None None None None None Mater Foundation†

Lindsay Mildenhall Middlemore Hospital None None None None None None NoneWendy M. Simon American Academy of

PediatricsNone None None None None None AAP staff†

Edgardo Szyld University of Oklahoma None None None None None None NoneMasanori Tamura Saitama Medical Center None None None None None None NoneSithembiso Velaphi Resuscitation Council of

Southern AfricaNone None None None None None None

Myra H. Wyckoff UT Southwestern None None None None None None None

This table represents the relationships of writing group members that may be perceived as actual or reasonably perceived conflicts of interest as reported on the Disclosure Questionnaire,which all members of the writing group are required to complete and submit. A relationship is considered to be “significant” if (a) the person receives $10,000 or more during any 12-monthperiod, or 5% or more of the person’s gross income; or (b) the person owns 5% or more of the voting stock or share of the entity, or owns $10,000 or more of the fair market value of the entity.A relationship is considered to be “modest” if it is less than “significant” under the preceding definition.* Modest.† Significant.

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APPENDIX

CoSTR Part 7: PICO Appendix

Part Task Force PICO ID Short Title PICO Question EvidenceReviewers

Part 7 NRP NRP 589 Temperature Maintenance in theDelivery Room—Prognosis

In nonasphyxiated babies at birth (P), does maintenance ofnormothermia (core temperature 36.5°C or greater and37.5°C or less) from delivery to admission (I), compared withhypothermia (less than 36°C) or hyperthermia (greater than37.5°C) (C), change survival to hospital discharge, respiratorydistress, survival to admission, hypoglycemia, intracranialhemorrhage, or infection rate (O)?

Jonathan Wyllie,Jeffrey Perlman

Part 7 NRP NRP 590 CPAP and IPPV—Intervention In spontaneously breathing preterm infants with respiratorydistress requiring respiratory support in the delivery room(P), does the use of CPAP (I), compared with intubation andIPPV (C), improve outcome (O)?

Tetsuya Isayama,Ben Stenson

Part 7 NRP NRP 599 Maintaining Infant TemperatureDuring Delivery RoomResuscitation—Intervention

Among preterm neonates who are under radiant warmers in thehospital delivery room (P), does increased room temperature,thermal mattress, or another intervention (I), compared withplastic wraps alone (C), reduce hypothermia (less than 36°C)on admission to neonatal intensive care unit (NICU) (O)?

Daniele Trevisanuto,Maria Fernandade Almeida

Part 7 NRP NRP 605 Thumb Versus 2-Finger Techniques forChest Compression—Intervention

In neonates receiving cardiac compressions (P), does the use ofa 2-thumb technique (I), compared with a 2-finger technique(C), result in return of spontaneous circulation (ROSC),improved neurologic outcomes, improved survival, improvedperfusion and gas exchange during CPR, and decreasedcompressor fatigue (O)?

Myra Wyckoff,LindsayMildenhall

Part 7 NRP NRP 618 Laryngeal Mask Airway—Intervention In newborn infants at near term (greater than 34 weeks) or termwho have indications for intermittent positive pressure forresuscitation (P), does use of a laryngeal mask as a primaryor secondary device (I), compared with mask ventilation orendotracheal intubation (C), improve response toresuscitation or change outcome (O), including indicators ofneonatal brain injury, achieving stable vital signs, increasingApgar scores, long-term outcomes, reducing the need forsubsequent intubation, or neonatal morbidity and mortality?

Edgardo Szyld,Enrique Udaeta

Part 7 NRP NRP 734 Limited-Resource–InducedHypothermia—Intervention

In term infants with moderate/severe hypoxic-ischemicencephalopathy managed in resource-limited countries (P),does therapeutic hypothermia to core temperature ofapproximately 33.5°C for 72 hours delivered by passivehypothermia and/or ice packs (I), versus standard therapy(C), improve the rates of death, neurodevelopmentalimpairments at 18 months to 2 years (O)?

Peter DavisJeffrey Perlman

Part 7 NRP NRP 738 Oxygen Delivery During CPR(Neonatal)—Intervention

In neonates receiving cardiac compressions (P), does 100% O2 asthe ventilation gas (I), compared with lower concentrations ofoxygen (C), increase survival rates, improve neurologicoutcomes, decrease time to ROSC, or decrease oxidativeinjury (O)?

Myra Wyckoff,LindsayMildenhall

Part 7 NRP NRP 787 Delayed Cord Clamping in Preterm InfantsRequiring Resuscitation (Intervention)

In preterm infants, including those who received resuscitation(P), does delayed cord clamping (greater than 30 seconds) (I),compared with immediate cord clamping (C), improvesurvival, long-term developmental outcome, cardiovascularstability, occurrence of intraventricular hemorrhage (IVH),necrotizing enterocolitis, temperature on admission toa newborn area, and hyperbilirubinemia (O)?

Masanori Tamura,Susan Niermeyer

Part 7 NRP NRP 793 Maintaining Infant TemperatureDuring Delivery RoomResuscitation—Intervention

In newborn infants (greater than 30 weeks of gestation) in low-resource settings during and/or after resuscitation/stabilization (P), does drying and skin-to-skin contact orcovering with plastic (I), compared with drying and no skin-to-skin or use of radiant warmer or incubator (C), change bodytemperature (O)?

Sithembiso Velaphi,Hege Ersdal,Nalini Singhal











Continued


Part 7 NRP NRP 804 Babies Born to Mothers Who AreHypothermic or Hyperthermic inLabor—Prognosis

In newborn babies (P), does maternal hypothermia orhyperthermia in labor (I), versus normal maternaltemperature (C), result in adverse neonatal effects (O)?Outcomes include mortality, neonatal seizures, and adverseneurologic states.

Henry Lee, MarilynEscobedo

Part 7 NRP NRP 805 Delivery Room Assessment for Less Than25 Weeks and Prognostic Score

In extremely preterm infants (less than 25 weeks) (P), doesdelivery room assessment with a prognostic score (I),compared with gestational age assessment alone (C), changesurvival to 18 to 22 months (O)?

Steven Ringer, SteveByrne

Part 7 NRP NRP 806 Newborn Infants Who Receive PPV forResuscitation, and Use of a Device toAssess Respiratory Function—Diagnostic

Innewborn infantswhoreceivePPV for resuscitation (P), doesuseof a device to assess respiratory function with or withoutpressure monitoring (I), compared with no device (C), changesurvival to hospital discharge with good neurologic outcome,IVH, time to heart rate greater than 100/min,bronchopulmonary dysplasia, pneumothorax (O)?

Helen Liley, VishalKapadia

Part 7 NRP NRP 809 Sustained Inflations—Intervention In term and preterm newborn infants who do not establishspontaneous respiration at birth (P), does administration of 1or more pressure-limited sustained lung inflations (I),compared with intermittent PPV with short inspiratory times(C), change Apgar score at 5 minutes, establishment of FRC,requirement for mechanical ventilation in first 72 hours, timeto heart rate greater than 100/min, rate of tracheal intubation,overall mortality (O)?

Jane McGowan,David Boyle

Part 7 NRP NRP 849 Umbilical Cord Milking—Intervention In very preterm infants (28weeksor less) (P), does umbilical cordmilking (I), in comparison with immediate umbilical cordclamping (C), affect death, neurodevelopmental outcome at 2to 3 years, cardiovascular stability, ie, need for pressors, needfor fluid bolus, initial mean blood pressure, IVH (any grade,severe grade), temperature on admission, hematologicindices (initial hemoglobin, need for transfusion),hyperbilirubinemia, need for phototherapy, or need forexchange transfusion (O)?

Marya Strand,Takahiro Sugiura

Part 7 NRP NRP 858 Warming of HypothermicNewborns—Intervention

In newbornswhoarehypothermic (temperature less than36.0°C)on admission (P), does rapid rewarming (I), compared withslow rewarming (C), change mortality rate, short and long-term neurologic outcome, hemorrhage, episodes of apneaand hypoglycemia, or need for respiratory support (O)?

Cheo Yeo, DanieleTrevisanuto

Part 7 NRP NRP 859 Resuscitation Training Frequency For course participants including (a) trainees and (b)practitioners (P), does frequent training (I), compared withless frequent training (annual or biennial) (C), change alllevels of education or practice, prevention of adverseoutcomes, overall mortality, scenario performance, medicalknowledge, psychomotor performance, provider confidence,course satisfaction (O)?

Chris Colby,Khalid Aziz

Part 7 NRP NRP 860 Predicting Death or Disability of Newbornsof Greater Than 34 Weeks Based on Apgarand/or Absence of Breathing—Prognosis

In newborn infants of greater than 34 weeks of gestation,receiving PPV at birth in settings where resources are limited(P), does presence of heart rate with no spontaneousbreathing or Apgar scores of 1 to 3 at greater than 5 minutespredict mortality or morbidity or cerebral palsy (O)?

Sithembiso Velaphi,Nalini Singhal,Hege Ersdal

Part 7 NRP NRP 862 Use of Feedback CPR Devices for NeonatalCardiac Arrest—Diagnostic

In asystolic/bradycardic neonates receiving cardiaccompressions (P), does the use of feedback devices such asend-tidal carbon dioxide (ETCO2) monitors, pulse oximeters, orautomated compression feedback devices (I), compared withclinical assessments of compression efficacy (C), decreasehands-off time, decrease time to ROSC, improve perfusion,increase survival rates, or improve neurologic outcomes (O)?

Lindsay Mildenhall,Takahiro Sugiura

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Continued


Part 7 NRP NRP 864 Oxygen Concentration for ResuscitatingPremature Newborns—Intervention

Among preterm newborns (less than 37 weeks of gestation) whoreceive PPV in the delivery room (P), does the use of high O2(50%–100%) as the ventilation gas (I), compared with lowconcentrations of O2 (21%–30%) (C), decrease mortality,decrease bronchopulmonary dysplasia, decrease retinopathy,decrease IVH (O)?

Gary Weiner,Douglas McMillan

Part 7 NRP NRP 865 Intubation and Tracheal Suctioning inNonvigorous Infants Born Though MSAFVersus No Intubation for TrachealSuctioning—Intervention

In nonvigorous infants at birth born through MSAF (P), doestracheal intubation for suctioning (I), compared with notracheal intubation (C), reduce meconium syndrome orprevent death (O)?

Sithembiso Velaphi,Jeffrey Perlman

Part 7 NRP NRP 867 Neonatal Resuscitation Instructors In neonatal resuscitation instructors (P), does formal training onspecific aspects of how to facilitate learning (I), comparedwith generic or nonspecific training (C), change clinicaloutcome, improve all levels of education or practice (O)?

Helen Liley, LouisHalamek

Part 7 NRP NRP 870 T-Piece Resuscitator and Self-InflatingBag—Intervention

In newborns (preterm and term) receiving ventilation (PPV)during resuscitation (P), does using a T-piece resuscitatorwith PEEP (I), compared with using a self-inflating bag withoutPEEP (C), achieve spontaneous breathing sooner and/orreduce the incidence of pneumothorax, bronchopulmonarydysplasia, and mortality (O)?

Yacov Rabi, HanSuk Kim

Part 7 NRP NRP 895 Chest Compression Ratio—Intervention In neonates receiving cardiac compressions (P), do other ratios(5:1, 9:3, 15:2, synchronous, etc) (I), compared with 3:1compressions to ventilations (C), increase survival rates,improve neurologic outcomes, improve perfusion and gasexchange during CPR, decrease time to ROSC, decrease tissueinjury, or decrease compressor fatigue (O)?

Qi Feng, MyraWyckoff

Part 7 NRP NRP 896 Apgar Score of 0 for 10 Minutes orLonger—Prognosis

In infants with a gestational age of 36 weeks or greater and anApgar score of 0 for 10 minutes or longer, despite ongoingresuscitation (P), what is the rate of survival to NICUadmission and death or neurocognitive impairment at 18 to22 months (O)?

Ruth Guinsburg,JaneMcGowan

Part 7 NRP NRP 897 Outcomes for PEEP Versus No PEEP in theDelivery Room—Intervention

In preterm/term newborn infants who do not establishrespiration at birth (P), does the use of PEEP as part of theinitial ventilation strategy (I), compared with no PEEP (C),improve Apgar score at 5 minutes, intubation in the deliveryroom, chest compressions in the delivery room, heart rategreater than 100/min by 2 minutes of life, time for heart rateto rise above 100/min, air leaks, oxygen saturation/oxygenation, FIO2 in the delivery room, mechanical ventilationin the first 72 hours, bronchopulmonary dysplasia, survival todischarge (O)?

Yacov Rabi, ColmO’Donnell

Part 7 NRP NRP 898 ECG/EKG (I) in Comparison to Oximetry orAuscultation for the Detection ofHeart Rate

In babies requiring resuscitation (P), does electrocardiography(ECG/EKG) (I), compared with oximetry or auscultation (C),measure heart rate faster and more accurately (O)?

Marya Strand, HegeErsdal










DOI: 10.1542/peds.2015-3373D2015;136;S120Pediatrics

Simon, Edgardo Szyld, Masanori Tamura and Sithembiso VelaphiM.Aziz, Ruth Guinsburg, Han-Suk Kim, Helen G. Liley, Lindsay Mildenhall, Wendy

Jeffrey M. Perlman, Jonathan Wyllie, John Kattwinkel, Myra H. Wyckoff, KhalidWith Treatment Recommendations (Reprint)

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DOI: 10.1542/peds.2015-3373D2015;136;S120Pediatrics

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