Am J Perinatol 2019; 36(S 02): S29-S32
DOI: 10.1055/s-0039-1691797
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Neonatal Resuscitation: State of the Art

Daniele Trevisanuto
1   Department of Woman's and Child's Health, University of Padova, Padova, Italy
,
Alfonso Galderisi
1   Department of Woman's and Child's Health, University of Padova, Padova, Italy
› Author Affiliations
Further Information

Address for correspondence

Daniele Trevisanuto, MD
Department of Woman's and Child's Health
University of Padova, Padova
Italy   

Publication History

Publication Date:
25 June 2019 (online)

 

Abstract

The objective of this study is to revise novel evidence and forthcoming clinical trials that focused on the gap of knowledge raised during the 2015 guidelines for neonatal resuscitation. Literature search on main topics on neonatal resuscitation published after 2015 edition of the consensus on science and guidelines was performed. Only relevant articles (mainly randomized controlled trials [RCTs] and meta-analyses) were included and presented as descriptive review. In the past years, new RCTs and/or meta-analyses have become available on umbilical cord clamping and umbilical cord milking, oxygen concentrations to start resuscitation in term and preterm infants, use of laryngeal mask, sustained lung inflation, less invasive surfactant administration, and heart rate assessment. Despite the increasing available literature on neonatal resuscitation in the past years, many interventions are still performed without robust scientific evidence. Adequately powered and well-designed RCTs are needed to optimize management of neonates at birth.


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The agenda of the International Liaison Committee on Resuscitation Neonatal Work Group relies on periodic consensus on science that revises novel evidence for the gap of knowledge in neonatal resuscitation and represents the basis for guidelines.[1] [2] [3] The consensus is expected to set the pace for forthcoming guidelines in a timely manner, as well as to encourage studies targeting critical areas for the lack of robust evidence or the absence of trials.

Herein, we revised novel evidence and forthcoming clinical trials that focused on the gap of knowledge raised during the 2015 guidelines as well as during the following consensus with the ultimate scope of providing an update in the initial steps of neonatal resuscitation (cord clamping and thermoregulation), ventilation and oxygenation, and heart rate (HR) assessment. These areas represented major gaps of knowledge in the past guidelines for neonatal resuscitation and have informed neonatal research of the past years.[1]

Each task has been described with respect to the examined gap of knowledge (“spotlight”), the “current recommendation,” and “novel evidence” in the area.

Cord Clamping and Initial Steps

Spotlight: Umbilical cord milking (UCM) and delayed cord clamping (DCC) to improve short-term neonatal outcomes and long-term neurodevelopment.

Current recommendations: Guidelines suggest “against” the routine use of cord milking for infants <29 weeks gestation, due to the lack of evidence for its benefit and acknowledge that “cord milking may be considered on an individualized basis or in a research setting as it may improve initial mean blood pressure, hematological indices and intracranial hemorrhage” with “no evidence for improvement or safety in long-term outcomes.”[1] DCC for longer than 30 seconds is recommended in both term and preterm infants who do not require resuscitation at birth[1] because it reduces intraventricular hemorrhage of any grade, the need for transfusion and the incidence of necrotizing enterocolitis,[1] in the absence of effect on long-term neurodevelopment. However, DCC is not recommended for infants requiring neonatal resuscitation due to the absence of studies including newborns requiring neonatal resuscitation.

Novel evidence: Katheria et al demonstrated that UCM increased language and cognitive scores at the 2-year Bayley scale evaluation in infants born <32 weeks' gestation, as compared with their peers managed with DCC, in a randomized controlled trial (RCT) conducted on 197 neonates.[4] Despite these results support UCM as an effective alternative to DCC, further research is needed to define the role of UCM on long-term outcomes.

Findings from a large Swedish longitudinal study reported that DCC improves fine motor and social domains at 4 years of age in full-term neonates, as assessed by the use of Wechsler Preschool and Primary Scale of Intelligence-III and Movement Assessment Battery for Children scores.[5] A recent meta-analysis on 18 RCTs conducted in 2,834 infants <37 week's gestation showed that DDC reduces hospital mortality of ∼30%. Same size effect was found in the subgroup of 996 infants ≤28 weeks' gestation.[6] This evidence is expected to strengthen the recommendation for DCC in preterm neonates.

In newborns born at term at risk for resuscitation, Katheria et al showed that 5-minute DCC could be accomplished safely without compromising the ability to perform resuscitation and was associated with increased saturations, decreased fractional cerebral tissue oxygen extraction, and greater blood pressure at 12 hours of life when compared with the group that received 1-minute DDC.[7] Despite these infants were considered at risk of resuscitation, their median (interquartile range) 5-minute Apgar score was 9 (9–9). Efficacy and safety of DDC in newborns needing resuscitation at birth remain to be established.[7]

Spotlight: Intrauterine thermostability” need to be replaced by extrauterine “thermoregulation” at birth by the use of differential strategies that include room temperature, radiant infant warmer, thermal mattress, plastic wrap, cap, and humidified and heated gases.[1] [8] The different contribution of each of them, as well as the new strategies to optimize thermoregulation after birth represent a current gap of knowledge.

Current recommendations: Hypothermia (<36°C) increases morbidity and mortality in preterm neonates[9] [10] [11]; therefore, guidelines recommend to maintain nonasphyxiated infants between 36.5 and 37.5°C.[1] Thermal mattress, plastic wrap, cap, and infant warmer, in addition to the environmental controlled temperature, are the tools to achieve such a goal. Their use (individual or combined) is recommended in infants less than 32 weeks' gestation, although the optimal intervention to achieve the established target is debated.[8] [12]

Novel evidence: Thermal servocontrol systems could represent a new promising instrument to achieve target temperature in delivery room. This system relies on a probe, positioned on newborn skin for temperature sensing, that drives automated adjustment of cradle temperature with a feedforward mechanism. A RCT in preterm neonates (birth weight less than 1,500 g and/or a gestational age less than 30 + 6 weeks) (NCT03844204) is ongoing. The primary outcome is the proportion of neonates in the normal thermal range (36.5–37.5°C) at neonatal intensive care unit (NICU) admission, and the intervention group will be positioned on the infant warmer with the servocontrol mechanism, while in the control group, the temperature of the infant warmer will be manually set at maximum of power output. This trial is expected to provide novel evidence regarding a new tool to achieve thermostability after delivery in preterm neonates. Indeed, it has been described how the relationship between admission temperature and morbidity/mortality is U-shaped with both hypothermia (<36.5°C) and hyperthermia (>37.2°C) is associated with adverse neonatal outcome.[11]


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Ventilation and Oxygenation

Spotlight: Optimizing need for initial oxygen concentrations in resuscitation of preterm newborns.

Current recommendations: During resuscitation of preterm neonates (<35 weeks' gestation), a lower oxygen concentration (21–30%) is recommended to initiate resuscitation. Higher oxygen concentrations are not recommended to prevent early exposure to additional oxygen in the absence of benefit.[1]

Novel evidence: A meta-analysis on 10 RCTs and 4 cohort studies including 5,697 preterm (<35 weeks' gestation) infants showed no statistically significant benefits or harms starting with lower FiO2 (≤0.50) compared with higher FiO2 (>0.50) in short-term and long-term mortalities, neurodevelopmental impairment, or other key preterm morbidities.[13] These results confirm 2015 recommendations that suggest starting resuscitation with low oxygen concentrations (FiO2 0.21–0.30), Of note, the majority of newborns ≤32 weeks' gestation will require oxygen supplementation at birth.

Spotlight: Optimizing interface for noninvasive ventilation.

Current recommendations: Guidelines suggest in favor of continuous positive airway pressure during neonatal resuscitation in spontaneously breathing term or preterm infant, while, in the absence of respiratory effort, positive end-expiratory pressure need to be considered. The lack of raise in HR remains the guide to evaluate the respiratory support intervention and to drive ventilation-corrective steps.[14] We fall short of evidence regarding the optimal interface to be used for the initial steps of neonatal resuscitation, although positive-pressure ventilation can be effectively delivered through flow-inflating bag, self-inflating bag, or T-piece resuscitator, with self-inflating bag to be considered only in the absence of compressed gas source. Alternative interfaces, as laryngeal mask airway (LMA) are indicated in late preterm and term infants,[1] although evidence for their use in smaller infants is lacking. The ideal noninvasive respiratory support, as well as the first choice interface, is still highly debated.

Novel evidence: A recent Cochrane review including seven RCTs (five comparing LMA with bag-mask ventilation and three comparing LMA with endotracheal tube) demonstrated that LMA reduced the need for intubation (5 studies, 661 infants), the ventilation times, and the admission to the NICU. In studies that allowed LMA rescue of infants failing with bag-mask ventilation, it was possible to avoid intubation in the majority.[15]

These findings confirm that LMA represents a useful emergency tool in delivery room and all health care providers should be trained on LMA use. Smaller sizes LMA for preterm infants are needed.

Spotlight: Sustained lung inflation (SLI).

Current recommendations: Current guidelines suggest against SLI for supporting preterm infants at birth.[1]

Novel evidence: SLI is not recommended after pivotal trial stopped for increased mortality.[16] Four hundred sixty infants born at less than 26 weeks' gestation failed to prove superiority of SLI as compared with intermittent positive pressure ventilation on the risk of bronchopulmonary dysplasia (BPD) or mortality at 36 weeks' gestation. Although the trial could have been underpowered for one of the two primary outcomes (BPD risk at 36 weeks' gestation), the increased mortality prevents SLI use in preterm infants.[17]

Spotlight: Less invasive surfactant administration (LISA) at birth.

Current recommendations: LISA allows surfactant administration by the insertion of a thin catheter in trachea in the absence of needing for intubation. LISA was associated with the lowest likelihood of the composite outcome of death or BPD at 36 weeks' postmenstrual age.[18] [19] While LISA is not mentioned in current neonatal guidelines, its use “should be considered” in spontaneously breathing preterm neonates with respiratory distress syndrome.[18]


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Heart Rate Assessment

Spotlight: HR is the most important clinical indicator during neonatal resuscitation. HR can be assessed by four modalities: umbilical cord palpation, palpation of peripheral pulses, auscultation by using stethoscope, and three-lead electrocardiogram (ECG).

Current recommendations: Three-lead ECG has been suggested after 2015 guidelines with very low quality of evidence, based on five nonrandomized clinical trials.[1] [2] Alternative ways to assess HR during neonatal resuscitation are a current gap of knowledge.

Novel evidence: Neo Tap Advanced Support (NeoTapAS) is a mobile application, based on a screen tapping method that calculates the HR. In a simulation study conducted on 160 measurements of HR, the mean difference between communicated and set HR was 1 beat per minute, suggesting NeoTap as a potential new tool to rapidly and accurately assess HR in delivery room.[20] In a neonatal resuscitation-simulated scenario, NeoTapAS reduced the time to the first HR communication and the time of initiation of chest compressions and administration of adrenaline compared with mental computation (NCT03730025).


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Conclusion

Consensus on science is an ongoing process and is the basis for forthcoming guidelines. Despite increasing literature on neonatal resuscitation has become available in the past years, many interventions are still performed without robust scientific evidence ([Table 1]). The knowledge of the gaps will help design large RCTs to optimize interventions in delivery room.

Table 1

Interventions, gaps of knowledge, novelties, and expected impact on future guidelines on neonatal resuscitation

Interventions

Gaps of knowledge

Novelties

Expected impact on future guidelines

Umbilical cord management

Cord clamping: DCC and milking

DCC improves long-term cognitive outcome in full-term infants; is feasible in neonates at risk of resuscitation; reduces mortality in preterm infants

UCM seems to improve long-term outcomes compared with DCC in preterm infants[7]

Initial steps

Temperature: lack of preferential strategy to optimize postnatal thermoregulation

Servocontrol system (NCT03844204)

Ongoing trial

Ventilation and initial oxygen concentrations

LMA in term and preterm infants

LMA reduces intubation, ventilatory times, and NICU admission compared with face mask[15]

SLI is not recommended

SLI increases mortality and does not improve BPD risk at 36 weeks[17]

Recommendation against SLI

Oxygen need: high or low FiO2?

Starting resuscitation with low FiO2 (≤0.50) or high FiO2 (>05.0) does not impact mortality and neurodevelopmental impairment[13]

Monitoring

HR assessment: three lead ECG has been suggested with low level of evidence

NeoTapAdvancedSupport[20] (NCT03730025)

New devices may help heart rate assessment and communication

Abbreviations: DCC, delayed cord clamping; ECG, electrocardiogram; HR, heart rate; LMA, laryngeal mask airway; NICU, neonatal intensive care unit; SLI, sustained lung inflation; UCM, umbilical cord milking.



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Conflict of Interest

None declared.

  • References

  • 1 Perlman JM, Wyllie J, Kattwinkel J. , et al; Neonatal Resuscitation Chapter Collaborators. Part 7: Neonatal Resuscitation: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation 2015; 132 (16) (Suppl. 01) S204-S241
  • 2 Wyckoff MH, Aziz K, Escobedo MB. , et al. Part 13: Neonatal Resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015; 132 (18) (Suppl. 02) S543-S560
  • 3 Wyllie J, Bruinenberg J, Roehr CC, Rüdiger M, Trevisanuto D, Urlesberger B. European Resuscitation Council Guidelines for Resuscitation 2015: Section 7. Resuscitation and support of transition of babies at birth. Resuscitation 2015; 95: 249-263
  • 4 Katheria A, Garey D, Truong G. , et al. A randomized clinical trial of umbilical cord milking vs delayed cord clamping in preterm infants: neurodevelopmental outcomes at 22-26 months of corrected age. J Pediatr 2018; 194: 76-80
  • 5 Andersson O, Lindquist B, Lindgren M, Stjernqvist K, Domellöf M, Hellström-Westas L. Effect of delayed cord clamping on neurodevelopment at 4 years of age: a randomized clinical trial. JAMA Pediatr 2015; 169 (07) 631-638
  • 6 Fogarty M, Osborn DA, Askie L. , et al. Delayed vs early umbilical cord clamping for preterm infants: a systematic review and meta-analysis. Am J Obstet Gynecol 2018; 218 (01) 1-18
  • 7 Katheria AC, Brown MK, Faksh A. , et al. Delayed cord clamping in newborns born at term at risk for resuscitation: a feasibility randomized clinical trial. J Pediatr 2017; 187: 313-317
  • 8 Trevisanuto D, Testoni D, de Almeida MFB. Maintaining normothermia: why and how?. Semin Fetal Neonatal Med 2018; 23 (05) 333-339
  • 9 Mullany LC, Katz J, Khatry SK, LeClerq SC, Darmstadt GL, Tielsch JM. Risk of mortality associated with neonatal hypothermia in southern Nepal. Arch Pediatr Adolesc Med 2010; 164 (07) 650-656
  • 10 Laptook AR, Salhab W, Bhaskar B. ; Neonatal Research Network. Admission temperature of low birth weight infants: predictors and associated morbidities. Pediatrics 2007; 119 (03) e643-e649
  • 11 Lyu Y, Shah PS, Ye XY. , et al; Canadian Neonatal Network. Association between admission temperature and mortality and major morbidity in preterm infants born at fewer than 33 weeks’ gestation. JAMA Pediatr 2015; 169 (04) e150277
  • 12 Perlman SB, Huppert TJ, Luna B. Functional near-infrared spectroscopy evidence for development of prefrontal engagement in working memory in early through middle childhood. Cereb Cortex 2016; 26 (06) 2790-2799
  • 13 Welsford M, Nishiyama C, Shortt C. , et al; International Liaison Committee on Resuscitation Neonatal Life Support Task Force. Room air for initiating term newborn resuscitation: a systematic review with meta-analysis. Pediatrics 2019; 143 (01) e20181825
  • 14 Escobedo MB, Shah BA, Song C, Makkar A, Szyld E. Recent recommendations and emerging science in neonatal resuscitation. Pediatr Clin North Am 2019; 66 (02) 309-320
  • 15 Qureshi MJ, Kumar M. Laryngeal mask airway versus bag-mask ventilation or endotracheal intubation for neonatal resuscitation. Cochrane Database Syst Rev 2018; 3: CD003314
  • 16 Foglia EE, Nolen TL, DeMauro SB. , et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Short-term outcomes of infants enrolled in randomized clinical trials vs those eligible but not enrolled. JAMA 2015; 313 (23) 2377-2379
  • 17 Kirpalani H, Ratcliffe SJ, Keszler M. , et al; SAIL Site Investigators. Effect of sustained inflations vs intermittent positive pressure ventilation on bronchopulmonary dysplasia or death among extremely preterm infants: the SAIL randomized clinical trial. JAMA 2019; 321 (12) 1165-1175
  • 18 Isayama T, Iwami H, McDonald S, Beyene J. Association of noninvasive ventilation strategies with mortality and bronchopulmonary dysplasia among preterm infants: a systematic review and meta-analysis. JAMA 2016; 316 (06) 611-624
  • 19 Aldana-Aguirre JC, Pinto M, Featherstone RM, Kumar M. Less invasive surfactant administration versus intubation for surfactant delivery in preterm infants with respiratory distress syndrome: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2017; 102 (01) F17-F23
  • 20 Binotti M, Cavallin F, Ingrassia PL. , et al. Heart rate assessment using NeoTapAdvancedSupport: a simulation study. Arch Dis Child Fetal Neonatal Ed 2018 . Doi: 10.1136/archdischild-2018-315408

Address for correspondence

Daniele Trevisanuto, MD
Department of Woman's and Child's Health
University of Padova, Padova
Italy   

  • References

  • 1 Perlman JM, Wyllie J, Kattwinkel J. , et al; Neonatal Resuscitation Chapter Collaborators. Part 7: Neonatal Resuscitation: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation 2015; 132 (16) (Suppl. 01) S204-S241
  • 2 Wyckoff MH, Aziz K, Escobedo MB. , et al. Part 13: Neonatal Resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015; 132 (18) (Suppl. 02) S543-S560
  • 3 Wyllie J, Bruinenberg J, Roehr CC, Rüdiger M, Trevisanuto D, Urlesberger B. European Resuscitation Council Guidelines for Resuscitation 2015: Section 7. Resuscitation and support of transition of babies at birth. Resuscitation 2015; 95: 249-263
  • 4 Katheria A, Garey D, Truong G. , et al. A randomized clinical trial of umbilical cord milking vs delayed cord clamping in preterm infants: neurodevelopmental outcomes at 22-26 months of corrected age. J Pediatr 2018; 194: 76-80
  • 5 Andersson O, Lindquist B, Lindgren M, Stjernqvist K, Domellöf M, Hellström-Westas L. Effect of delayed cord clamping on neurodevelopment at 4 years of age: a randomized clinical trial. JAMA Pediatr 2015; 169 (07) 631-638
  • 6 Fogarty M, Osborn DA, Askie L. , et al. Delayed vs early umbilical cord clamping for preterm infants: a systematic review and meta-analysis. Am J Obstet Gynecol 2018; 218 (01) 1-18
  • 7 Katheria AC, Brown MK, Faksh A. , et al. Delayed cord clamping in newborns born at term at risk for resuscitation: a feasibility randomized clinical trial. J Pediatr 2017; 187: 313-317
  • 8 Trevisanuto D, Testoni D, de Almeida MFB. Maintaining normothermia: why and how?. Semin Fetal Neonatal Med 2018; 23 (05) 333-339
  • 9 Mullany LC, Katz J, Khatry SK, LeClerq SC, Darmstadt GL, Tielsch JM. Risk of mortality associated with neonatal hypothermia in southern Nepal. Arch Pediatr Adolesc Med 2010; 164 (07) 650-656
  • 10 Laptook AR, Salhab W, Bhaskar B. ; Neonatal Research Network. Admission temperature of low birth weight infants: predictors and associated morbidities. Pediatrics 2007; 119 (03) e643-e649
  • 11 Lyu Y, Shah PS, Ye XY. , et al; Canadian Neonatal Network. Association between admission temperature and mortality and major morbidity in preterm infants born at fewer than 33 weeks’ gestation. JAMA Pediatr 2015; 169 (04) e150277
  • 12 Perlman SB, Huppert TJ, Luna B. Functional near-infrared spectroscopy evidence for development of prefrontal engagement in working memory in early through middle childhood. Cereb Cortex 2016; 26 (06) 2790-2799
  • 13 Welsford M, Nishiyama C, Shortt C. , et al; International Liaison Committee on Resuscitation Neonatal Life Support Task Force. Room air for initiating term newborn resuscitation: a systematic review with meta-analysis. Pediatrics 2019; 143 (01) e20181825
  • 14 Escobedo MB, Shah BA, Song C, Makkar A, Szyld E. Recent recommendations and emerging science in neonatal resuscitation. Pediatr Clin North Am 2019; 66 (02) 309-320
  • 15 Qureshi MJ, Kumar M. Laryngeal mask airway versus bag-mask ventilation or endotracheal intubation for neonatal resuscitation. Cochrane Database Syst Rev 2018; 3: CD003314
  • 16 Foglia EE, Nolen TL, DeMauro SB. , et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Short-term outcomes of infants enrolled in randomized clinical trials vs those eligible but not enrolled. JAMA 2015; 313 (23) 2377-2379
  • 17 Kirpalani H, Ratcliffe SJ, Keszler M. , et al; SAIL Site Investigators. Effect of sustained inflations vs intermittent positive pressure ventilation on bronchopulmonary dysplasia or death among extremely preterm infants: the SAIL randomized clinical trial. JAMA 2019; 321 (12) 1165-1175
  • 18 Isayama T, Iwami H, McDonald S, Beyene J. Association of noninvasive ventilation strategies with mortality and bronchopulmonary dysplasia among preterm infants: a systematic review and meta-analysis. JAMA 2016; 316 (06) 611-624
  • 19 Aldana-Aguirre JC, Pinto M, Featherstone RM, Kumar M. Less invasive surfactant administration versus intubation for surfactant delivery in preterm infants with respiratory distress syndrome: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 2017; 102 (01) F17-F23
  • 20 Binotti M, Cavallin F, Ingrassia PL. , et al. Heart rate assessment using NeoTapAdvancedSupport: a simulation study. Arch Dis Child Fetal Neonatal Ed 2018 . Doi: 10.1136/archdischild-2018-315408