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Initial Oxygen Concentration for Preterm Neonatal Resuscitation: (NLS 864) Systematic Review

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Initial Oxygen Concentration for Preterm Neonatal Resuscitation

Citation

Roehr CC, Weiner GM, Isayama T, Dawson JA, Rabi Y, Kapadia VS, de Almeida MF, Trevisanuto D, Mildenhall L, Liley HG, Hosono S, Kim HS, Szyld E, Perlman JM, Aziz K, Velaphi S, Guinsburg R, Welsford M, Nishiyama C, Wyllie JP and Wyckoff MH. Initial oxygen concentration for preterm neonatal resuscitation [Internet] Brussels, Belgium: International Liaison Committee on Resuscitation (ILCOR) Neonatal Life Support Task Force, November 16, 2018

Available from: http://ilcor.org

Methodological Preamble and Link to Published Systematic Review

The continuous evidence process for the production of Consensus of Science and Treatment Recommendations (CoSTR) started with a systematic review regarding oxygen use in the delivery room for preterm infants (Welsford M, 2018, PROSPERO CRD42018084902 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=84902) conducted by Dr. Michelle Welsford, McMaster University, Canada with involvement of clinical content experts. Evidence for neonatal literature was sought and considered by the Neonatal Life Support Task Force. These data were taken into account when formulating the Treatment Recommendations.

Systematic Review

Welsford M, Nishiyama C, Shortt C, Weiner G, Roehr CC, Isayama T, Dawson JA, Wyckoff MH, Rabi Y on behalf of the International Liaison Committee on Resuscitation Neonatal Life Support Task Force. Initial oxygen use for preterm newborn resuscitation: a systematic review with meta-analysis. Pediatrics on-line Dec 21, 2018. DOI: 10.1542/peds.2018-1828

Initial Oxygen Concentration for Preterm Neonatal Resuscitation PICOST:

The PICOST (Population, Intervention, Comparator, Outcome, Study Designs, and Time Frame)

Population: Preterm newborn infants (<35 weeks estimated gestational age) who receive respiratory support at birth

Intervention: Lower initial oxygen concentration

Comparison: Higher initial oxygen concentration

Outcomes:

Primary:

  • All cause short-term mortality (in-hospital or 30 days)

Secondary:

  • All cause long-term mortality (1-3 years)
  • Long-term neurodevelopmental impairment (1-3 years)
  • Retinopathy of prematurity
  • Necrotizing enterocolitis
  • Bronchopulmonary dysplasia
  • Major intraventricular hemorrhage (grade III/IV)
  • Time to heart rate >100 bpm

Study Designs: Randomized controlled trials (RCT), quasi-randomized controlled trials (qRCT), and non-randomised cohort studies were included. Excluded animal studies, unpublished studies (e.g., conference abstracts).

Timeframe: 1980 to August 10, 2018

A priori subgroups to be examined: gestational age (≤32 weeks, ≤28 weeks); grouped lower and higher oxygen concentrations (FiO2 0.21 compared to 1.0 only, FiO2 0.21-0.3 compared to 0.8-1.0 only, FiO2 0.3-0.9-1.0, FiO2 0.5 compared to 1.0, FiO2 0.3 compared to 0.6-0.65); explicit oxygen saturation targeting vs no oxygen saturation targeting

PROSPERO Registration: CRD42018084902

Consensus on Science

All Preterm Gestational Ages Combined (<35 weeks gestation):

For the critical outcome of all cause short-term mortality (in-hospital or 30 days), the evidence of very low certainty (downgraded for risk of bias and imprecision) from 10 RCTs with 968 newborns <35 weeks gestation receiving respiratory support at birth showed no benefit or harm of lower initial oxygen concentration compared to higher initial oxygen concentration (RR=0.83 95% CI 0.50-1.37; I2=18%); 15/1000 fewer newborns with short term mortality when lower compared to higher initial oxygen concentration was used [95% CI: 44/1000 fewer to 32/1000 more] (Lundstrom 1995 F81; Harling 2005 F401; Wang 2009 1083; Vento 2009 e439; Rabi 2011 374; Armanian 2012 25; Kapadia 2013 e1488; Aguar 2013 abstract; Rook 2014 1322; Oei 2017 e20161452).

For the critical outcome of all cause long-term mortality (1-3 years), the evidence of very low certainty (downgraded for risk of bias, inconsistency, and imprecision) from 3 RCTs (two were combined in one publication) with 491 newborns <35 weeks gestation receiving respiratory support at birth showed no benefit or harm of lower initial oxygen concentration compared to higher initial oxygen concentration (RR=1.05 95% CI 0.32-3.39; I2=79%); 5/1000 more newborns with long-term mortality when lower compared to higher initial oxygen concentration was used [95%CI: 71/1000 fewer to 248/1000 more] (Boronat 2016 e20161405; Thamrin 2018 55).

For the critical outcome of all cause long-term mortality (1-3 years), the evidence of very low certainty (downgraded for risk of bias) from 2 observational cohort studies with 1225 newborns <35 weeks gestation receiving respiratory support at birth showed benefit of lower initial oxygen concentration compared to higher initial oxygen concentration (RR=0.77 95% CI 0.59-0.99; I2=6%); 48/1000 fewer with long-term mortality when lower initial oxygen concentration compared to higher initial oxygen concentration was used [95% CI: 86/1000 fewer to 2/1000 fewer] (Kapadia 2017 35; Soraisham 2017 1141).

For the critical outcome of long-term neurodevelopmental impairment (NDI, moderate-severe,1-3 years) the evidence of very low certainty (downgraded for risk of bias, inconsistency, and imprecision) from 3 RCTs (one combined publication) with 389 newborns <35 weeks gestation receiving respiratory support at birth showed no benefit or harm of lower initial oxygen concentration compared to higher initial oxygen concentration (RR=1.14 95% CI 0.78-1.67; I2=0); 27/1000 more with NDI when lower initial oxygen concentration compared to higher initial oxygen concentration was used [95% CI: 42/1000 fewer to 129/1000 more] (Boronat 2016 e20161405; Thamrin 2018 55).

For the critical outcome of long-term neurodevelopmental impairment (NDI, moderate-severe, 1-3 years) the evidence of very low certainty (downgraded for risk of bias, inconsistency, and imprecision) from 2 observational cohort studies with 930 newborns <35 weeks gestation receiving respiratory support at birth showed no benefit or harm of lower initial oxygen concentration compared to higher initial oxygen concentration (RR=0.89 95% CI 0.66-1.20; I2=59%); 53/1000 fewer with NDI when lower initial oxygen concentration compared to higher initial oxygen concentration was used [95% CI: 165/1000 fewer to 97/1000 more] (Kapadia 2017 35; Soraisham 2017 1141).

For the critical outcome of retinopathy of prematurity (Grade III-V), the evidence of very low certainty (downgraded for risk of bias and imprecision) from 7 RCTs with 806 newborns <35 weeks gestation receiving respiratory support at birth showed no benefit or harm of lower initial oxygen concentration compared to higher initial oxygen concentration (RR=0.73 95% CI 0.42-1.27; I2=0%); 19/1000 fewer with retinopathy of prematurity (Grade III-V) when lower initial oxygen concentration compared to higher initial oxygen concentration was used [95% CI: 42/1000 fewer to 19/1000 more] (Lundstrom 1995 F81; Harling 2005 F401; Vento 2009 e439; Kapadia 2013 e1488; Aguar 2013 abstract; Rook 2014 1322; Oei 2017 e20161452).

For the critical outcome of necrotizing enterocolitis (Bell’s Grade II-III), the evidence of very low certainty (downgraded for risk of bias and imprecision) from 8 RCTs with 847 newborns <35 weeks gestation receiving respiratory support at birth showed no benefit or harm of lower initial oxygen concentration compared to higher initial oxygen concentration (RR=1.34 95% CI 0.63-2.84; I2=0%); 12/1000 more with necrotizing enterocolitis when lower initial oxygen concentration compared to higher initial oxygen concentration was used [95% CI: 13/1000 fewer to 65/1000 more] (Lundstrom 1995 F81; Harling 2005 F401; Wang 2008 1083; Vento 2009 e439; Kapadia 2013 e1488; Aguar 2013 abstract; Rook 2014 1322; Oei 2017 e20161452).

For the critical outcome of bronchopulmonary dysplasia (moderate to severe), the evidence of very low certainty (downgraded for risk of bias and imprecision) from 8 RCTs with 843 newborns <35 weeks gestation receiving respiratory support at birth showed no benefit or harm of lower initial oxygen concentration compared to higher initial oxygen concentration (RR=1.00 95% CI 0.71-1.40; I2=47%); 0/1000 fewer with bronchopulmonary dysplasia when lower initial oxygen concentration compared to higher initial oxygen concentration was used [95% CI: 77/1000 fewer to 107/1000 more] (Harling 2005 F401; Wang 2008 1083; Vento 2009 e439; Rabi 2011 252; Kapadia 2013 e1488; Aguar 2013 abstract; Rook 2014 1322; Oei 2017 e20161452).

For the critical outcome of major intraventricular hemorrhage (Grade III-IV), the evidence of very low certainty (downgraded for risk of bias and imprecision) from 7 RCTs with 795 newborns <35 weeks gestation receiving respiratory support at delivery showed no benefit or harm of lower initial oxygen concentration compared to higher initial oxygen concentration (RR=0.96 95% CI 0.61-1.51; I2=0%); 3/1000 fewer with major intraventricular hemorrhage (Grade III-IV) when lower initial oxygen concentration compared to higher initial oxygen concentration was used [95% CI: 32/1000 fewer to 42/1000 more] (Lundstrom 1995 F81; Wang 2009 1083; Vento 2009 e439; Kapadia 2013 e1488; Aguar 2013 abstract; Rook 2014 1322; Oei 2017 e20161452).

For the important outcome of time to heart rate > 100 bpm post-delivery, limited direct evidence for newborns <35 weeks gestation was found such that meta-analysis was precluded.

Subgroup Newborns ≤32 Weeks Gestation

For the critical outcome of all cause short-term mortality (in-hospital or 30 days), the evidence of very low certainty (downgraded for risk of bias and imprecision) from 8 RCTs with 837 newborns ≤32 weeks gestation receiving respiratory support at birth showed no benefit or harm of lower initial oxygen concentration compared to higher initial oxygen concentration (RR=0.93 95% CI 0.55-1.55; I2=15%); 6/1000 fewer with short-term mortality when lower initial oxygen concentration compared to higher initial oxygen concentration was used [95% CI: 39/1000 fewer to 47/1000 more] (Harling 2005 F401; Wang 2009 1083; Vento 2009 e439; Rabi 2011 e374; Kapadia 2013 e1488; Aguar 2013 abstract; Rook 2014 1322; Oei 2017 e20161452).

For the critical outcome of all cause long-term mortality (1-3 years) in newborns ≤32 weeks gestation, the results are the same as for <35 weeks gestation.

For the critical outcome of long-term neurodevelopmental impairment (NDI, moderate-severe, 1-3 years) in newborns ≤32 weeks gestation, the results are the same as for <35 weeks gestation.

Subgroup Newborns ≤28 Weeks Gestation

For the critical outcome of all cause short-term mortality (in-hospital or 30 days), the evidence of very low certainty (downgraded for risk of bias, inconsistency, and imprecision) from 7 RCTs with 467 newborns ≤28 weeks gestation receiving respiratory support at birth showed no benefit or harm of lower initial oxygen concentration compared to higher initial oxygen concentration (RR=0.92 95% CI 0.43-1.94; I2=45%); 10/1000 fewer with short-term mortality when lower initial oxygen concentration compared to higher initial oxygen concentration was used [95% CI: 70/1000 fewer to 116/1000 more] (Wang 2009 1083; Vento 2009 e439; Rabi 2011 e374; Kapadia 2013 e1488; Aguar 2013 abstract; Rook 2014 1322; Oei 2017 e20161452).

For the critical outcome of all cause long-term mortality (1-3 years), the evidence of very low certainty (downgraded for risk of bias, inconsistency, and imprecision) from 1 RCT with 86 newborns ≤28 weeks gestation receiving respiratory support at birth showed no benefit or harm of lower initial oxygen concentration compared to higher initial oxygen concentration (RR=2.11 95% CI 0.86-5.19; I2=N/A); 145/1000 more with long-term mortality when lower initial oxygen concentration compared to higher initial oxygen concentration was used [95% CI: 18/1000 fewer to 547/1000 more] (Thamrin 2018 55).

For the critical outcome of all cause long-term mortality (1-3 years), the evidence of very low certainty (downgraded for risk of bias) from 2 observational cohort studies with 1225 newborns ≤28 weeks gestation receiving respiratory support at birth showed benefit of lower initial oxygen concentration compared to higher initial oxygen concentration (RR=0.77 95% CI 0.59-0.99; I2=6%); 48/1000 fewer with long-term mortality when lower initial oxygen concentration compared to higher initial oxygen concentration was used [95% CI: 86/1000 fewer to 2/1000 fewer] (Kapadia 2017 35; Soraisham 2017 1141).

For the critical outcome of long-term neurodevelopmental impairment (NDI, moderate-severe, 1-3 years) evidence of very low certainty (downgraded for risk of bias, inconsistency and imprecision) from 1 RCT with 69 newborns ≤28 weeks gestation receiving respiratory support at birth showed no benefit or harm of lower initial oxygen concentration compared to higher initial oxygen concentration (RR 1.08 95% CI 0.58-2.03; I2=N/A); 28/1000 more with long-term neurodevelopmental impairment with lower initial oxygen concentration compared to higher initial oxygen concentration was used [95% CI: 147/1000 fewer to 360/1000 more] (Thamrin 2018 55).

For the critical outcome of retinopathy of prematurity (Grade III-V), the evidence of very low certainty (downgraded for risk of bias and imprecision) from 6 RCTs with 441 newborns ≤28 weeks gestation receiving respiratory support at birth showed no benefit or harm of lower initial oxygen concentration compared to higher initial oxygen concentration (RR=0.75 95% CI 0.43-1.33; I2=0%); 30/1000 fewer with retinopathy of prematurity when lower initial oxygen concentration compared to higher initial oxygen concentration was used [95% CI: 67/1000 fewer to 39/1000 more] (Wang 2008 1083; Vento 2009 e439; Kapadia 2013 e1488; Aguar 2013 abstract; Rook 2014 1322; Oei 2017 e20161452).

For the critical outcome of necrotizing enterocolitis (Bell’s Grade II-III), the evidence of very low certainty (downgraded for risk of bias and imprecision) from 6 RCTs with 441 newborns ≤28 weeks gestation receiving respiratory support at birth showed no benefit or harm of lower initial oxygen concentration compared to higher initial oxygen concentration (RR=1.62 95% CI 0.66-3.99; I2=0%); 20/1000 more with necrotizing enterocolitis when lower initial oxygen concentration compared to higher initial oxygen concentration was used [95% CI: 11/1000 fewer to 95/1000 more] (Wang 2008 1083; Vento 2009 e439; Kapadia 2013 e1488; Aguar 2013 abstract; Rook 2014 1322; Oei 2017 e20161452).

For the critical outcome of bronchopulmonary dysplasia (moderate to severe), the evidence of very low certainty (downgraded for risk of bias and imprecision) from 7 RCTs with 467 newborns ≤28 weeks gestation receiving respiratory support at birth showed no benefit or harm of lower initial oxygen concentration compared to higher initial oxygen concentration (RR=0.90 95% CI 0.64-1.28; I2=31%); 37/1000 fewer with bronchopulmonary dysplasia when lower initial oxygen concentration compared to higher initial oxygen concentration was used [95% CI: 132/1000 fewer to 102/1000 more] (Wang 2008 1083; Vento 2009 e439; Rabi 2011 e374; Kapadia 2013 e1488; Aguar 2013 abstract; Rook 2014 1322; Oei 2017 e20161452).

For the critical outcome of major intraventricular hemorrhage (Grade III-IV), the evidence of very low certainty (downgraded for risk of bias and imprecision) from 6 RCTs with 441 newborns ≤28 weeks gestation receiving respiratory support at birth showed no benefit or harm of lower initial oxygen concentration compared to higher initial oxygen concentration (RR=0.84 95% CI 0.50-1.40; I2=12%); 23/1000 fewer with major intraventricular hemorrhage (Grade III-IV) when lower initial oxygen concentration compared to higher initial oxygen concentration was used [95% CI: 73/1000 fewer to 58/1000 more] (Wang 2009 1083; Vento 2009 e439; Kapadia 2013 e1488; Aguar 2013 abstract; Rook 2014 1322; Oei 2017 e20161452).

Subgroup FiO2 0.21 Compared to FiO2 1.00 (<35 weeks gestation)

For the critical outcome of all cause short-term mortality (in-hospital or 30 days), the evidence of very low certainty (downgraded for risk of bias and imprecision) from 4 RCTs with 484 newborns <35 weeks gestation receiving respiratory support at birth showed no benefit or harm of initial room air compared to initial 100% oxygen concentration (RR=1.58 95% CI 0.70-3.55; I2=4%); 26/1000 more with short-term mortality when lower initial oxygen concentration compared to higher initial oxygen concentration was used [95% CI: 14/1000 fewer to 115/1000 more] (Wang 2009 1083; Rabi 2011 e374; Kapadia 2013 e1488; Oei 2017 e20161452).

For the critical outcome of all cause long-term mortality (1-3 years), in newborns ≤35 weeks gestation results are the same as for all groups <35 weeks gestation.

For the critical outcome of long-term neurodevelopmental impairment (NDI, moderate-severe, 1-3 years) in preterm newborns (<35 weeks gestation), the results are the same as for all groups <35 weeks gestation.

Subgroup FiO2 0.21-0.30 Compared to FiO2 0.80-1.00 (<35 weeks gestation)

For the critical outcome of all cause short-term mortality (in-hospital or 30 days), the evidence of very low certainty (downgraded for risk of bias and imprecision) from 7 RCTs with 667 preterm newborns <35 weeks gestation receiving respiratory support at birth showed no benefit or harm of 21-30% initial oxygen concentration compared to 80-100% initial oxygen concentration (RR=1.24 95% CI 0.61-2.49; I2=13%); 13/1000 more with short-term mortality when lower initial oxygen concentration compared to higher initial oxygen concentration was used [95% CI: 22/1000 fewer to 83/1000 more] (Lundstrom 1995 F81; Wang 2009 1083; Vento 2009 e439; Rabi 2011 e374; Armanian 2012 25; Kapadia 2013 e1488; Oei 2017 e20161452).

For the critical outcome of all cause long-term mortality (1-3 years), in newborns ≤35 weeks gestation results are the same as for all groups <35 weeks gestation.

For the critical outcome of long-term neurodevelopmental impairment (NDI, moderate-severe, 1-3 years) in preterm newborns (<35 weeks gestation), the results are the same as for all groups <35 weeks gestation.

Subgroup FiO2 0.30 Compared to FiO2 0.90-1.00 (<35 weeks gestation)

For the critical outcome of all cause short-term mortality (in-hospital or 30 days), the evidence of very low certainty (downgraded for risk of bias, inconsistency, and imprecision) from 2 RCTs with 110 newborns <35 weeks gestation receiving respiratory support at birth showed no benefit or harm of 30% initial oxygen concentration compared to 90-100% initial oxygen concentration (RR=1.48 95% CI 0.35-6.17; I2=N/A); 25/1000 more with short-term mortality when lower initial oxygen concentration compared to higher initial oxygen concentration was used [95% CI: 34/1000 fewer to 272/1000 more] (Vento 2009 e439; Armanian 2012 25).

There is no data on long-term mortality or neurodevelopmental impairment for this subgroup.

Subgroup FiO2 0.30 Compared to FiO2 0.60-0.65 (<35 weeks gestation)

For the critical outcome of all cause short-term mortality (in-hospital or 30 days), the evidence of moderate certainty (downgraded for imprecision) from 2 RCTs with 253 newborns <35 weeks gestation receiving respiratory support at birth showed no benefit or harm of 30% initial oxygen concentration compared to 60-65% initial oxygen concentration (RR=0.51 95% CI 0.24-1.06; I2=0%); 69/1000 fewer with short-term mortality when lower initial oxygen concentration compared to higher initial oxygen concentration was used [95% CI: 108/1000 fewer to 9/1000 more] (Rook 2014 1322; Aguar 2013 abstract).

For the critical outcome of all cause long-term mortality (1-3 years), the evidence of low certainty (downgraded for inconsistency, and imprecision) from 2 RCTs (one combined publication) with 253 newborns <35 weeks gestation receiving respiratory support at birth showed no benefit or harm of 30% initial oxygen concentration compared to 60-65% initial oxygen concentration (RR=0.58 95% CI 0.28-1.20; I2=N/A); 60/1000 fewer with long-term mortality when lower initial oxygen concentration compared to higher initial oxygen concentration was used [95% CI: 102/1000 fewer to 28/1000 more] (Boronat 2016 e20161405).

For the critical outcome of long-term neurodevelopmental impairment (NDI, moderate-severe, 1-3 years) the combined evidence of low certainty (downgraded for inconsistency and imprecision) from 2 RCTs (one combined publication) with 174 newborns <35 weeks gestation receiving respiratory support at birth showed no benefit or harm of 30% initial oxygen concentration compared to 60-65% initial oxygen concentration (RR=0.96 95% CI 0.38-2.43; I2=N/A); 4/1000 fewer with long-term neurodevelopmental impairment when lower initial oxygen concentration compared to higher initial oxygen concentration was used [95% CI: 58/1000 fewer to 135/1000 more] (Boronat 2016 e20161405).

Subgroup FiO2 0.50 Compared to FiO2 1.00 (<35 weeks gestation)

For the critical outcome of all cause short-term mortality (in-hospital or 30 days), the evidence of very low certainty (downgraded for inconsistency and imprecision) from 1 RCT with 52 newborns <35 weeks gestation receiving respiratory support at birth showed no benefit or harm of 50% initial oxygen concentration compared to 100% initial oxygen concentration (RR=0.80 95% CI 0.24-2.65; I2=N/A); 38/1000 fewer with short-term mortality when lower initial oxygen concentration compared to higher initial oxygen concentration was used [95% CI: 146/1000 fewer to 317/1000 more] (Harling 2005 F401).

There is no data on long-term mortality or neurodevelopmental impairment for this subgroup.

Subgroup No Explicit Oxygen Saturation Targeting (<35 weeks gestation)

For the critical outcome of all cause short-term mortality (in-hospital or 30 days), the evidence of very low certainty (downgraded for risk of bias and imprecision) from 2 RCTs with 121 newborns <35 weeks gestation receiving respiratory support at birth showed no benefit or harm of low initial oxygen concentration compared to high initial oxygen concentration when no explicit oxygen saturation targeting was used. (RR=0.58 95% CI 0.23-1.49; I2=0%); 76/1000 fewer with short-term mortality when lower initial oxygen concentration compared to higher initial oxygen concentration was used [95% CI: 139/1000 fewer to 88/1000 more] (Lundstrom 1995 F81; Harling 2005 F401).

There is no data on long-term mortality or neurodevelopmental impairment for this subgroup.

Subgroup with Oxygen Saturation Targeting (<35 weeks gestation)

For the critical outcome of all cause short-term mortality (in-hospital or 30 days), the evidence of very low certainty (downgraded for risk of bias and imprecision) from 8 RCTs with 847 newborns <35 weeks gestation receiving respiratory support at birth showed no benefit or harm of lower initial oxygen concentration compared to higher initial oxygen concentration when oxygen saturation targeting was used (RR=0.92 95% CI 0.50-1.71; I2=28%); 6/1000 fewer with short-term mortality when lower initial oxygen concentration compared to higher initial oxygen concentration was used [95% CI: 37/1000 fewer to 52/1000 more] (Wang 2009 1083; Vento 2009 e439; Rabi 2011 e374; Armanian 2012 25; Kapadia 2013 e1488; Aguar 2013 abstract; Rook 2014 1322; Oei 2017 e20161452).

For the critical outcome of long-term mortality (1-3 years) in preterm newborns the results are the same as for all groups <35 weeks gestation.

For the critical outcome of long-term neurodevelopmental impairment (NDI, moderate-severe, 1-3 years) in newborns <35 weeks gestation, the results are the same as for all groups < 35 weeks gestation.

Treatment Recommendations

We suggest starting with a lower oxygen concentration (21-30%) compared to higher oxygen concentration (60-100%) for preterm (<35 weeks gestation) newborns who receive respiratory support at birth with subsequent titration of oxygen concentration using pulse oximetry (weak recommendation, very low certainty of evidence).

Justifications and Evidence to Decision Highlights

Balancing the benefits and serious potential harm of low versus high oxygen concentrations in neonatal care is a ubiquitous concern, particularly for preterm infants as decades of research demonstrate that oxygen exposure is a determinant of critical neonatal outcomes in preterm infants. Concern remains that the oxygen concentrations to which preterm infants are first exposed if they need resuscitation immediately after birth may be a critical contributor to outcomes regardless of subsequent oxygen exposure. Both parents and clinicians rate the outcomes assessed in this systematic review as either critical or important. For all the critical outcomes assessed in the meta-analyses of RCTs, the 95% confidence intervals of relative risks were wide enough to include both potential harm as well as potential benefit. Thus, it is unclear whether initial low (or high) oxygen concentrations may have undesirable effects. In still suggesting to start with low oxygen concentrations, we place value on avoiding exposure of preterm babies to additional oxygen without proven benefit for critical or important outcomes, as we are cognizant of harms in preterm animals and increased neonatal mortality in term infants exposed to high initial O2 concentration.

We recognize that no studies have compared the safety or efficacy of commencing resuscitation in 21% versus intermediate concentrations such as 30% oxygen; however, nearly all preterm babies whose respiratory support was initiated with 21% oxygen subsequently received additional oxygen (30-40%) to meet empiric oxygen saturation targets. We emphasize that the included studies only measured the effect of varying initial inspired oxygen concentrations and were not designed to assess the safety or efficacy of different oxygen saturation targets.

The feasibility and acceptability among clinicians of initiating resuscitation with 21-30% oxygen has been demonstrated: most respondents to a recent international survey were already avoiding a high initial oxygen concentration strategy (such as 100% oxygen) during preterm newborn resuscitation and stabilization. Although there are no published economic analyses, it is likely that use of low FiO2 does not add cost. In well-resourced perinatal care settings, the cost of pulse oximetry, blenders, and gas lines would probably be the same regardless of the initial oxygen concentration. However, in poorly resourced settings, it is the availability of human resources, gases, and equipment that will determine the immediate financial impact of this suggestion/recommendation. The overall cost-effectiveness of this suggestion/recommendation cannot currently be estimated as there is no evidence in relation to long-term outcomes and their cost.

Knowledge Gaps

  • As the 95% CI for the primary outcome includes both harm and benefit, further, high quality studies are needed to determine the effect size more precisely.
  • Need long term NDI outcomes from more randomized studies.
  • Current studies have not adequately addressed the possible oxygen requirements for specific gestational age groups
  • Oxygen targets for preterm infants remain unknown
  • How to best titrate oxygen in the delivery room for preterm infants is unknown
  • Information regarding how cord clamping management impacts oxygen use following birth is needed

Attachments

EtD Table: Should Low FiO2 vs High FiO2 be used for Preterm Neonatal Resuscitation?

References

  • Aguar M, Escobar J, Kuligowski J, Inondo M, Izquierdo M, Nunez A, et al. Preterm babies randomly assigned to be blindly resuscitated with higher (60%) vs. lower (30%) initial FiO2: effects on oxidative stress and mortality. Pediatric Academic Societies Annual Meeting; Vancouver 2013 (abstract).
  • Armanian AM, Badiee Z. Resuscitation of preterm newborns with low concentration oxygen versus high concentration oxygen. J Res Pharm Pract. 2012 Jul;1(1):25–9.
  • Boronat N, Aguar M, Rook D, Iriondo M, Brugada M, Cernada M, et al. Survival and Neurodevelopmental Outcomes of Preterms Resuscitated With Different Oxygen Fractions. Pediatrics. 2016 Dec;138(6):1–11.
  • Dawson JA, Kamlin COF, Wong C, Pas te AB, O'Donnell CPF, Donath SM, et al. Oxygen saturation and heart rate during delivery room resuscitation of infants. Arch Dis Child Fetal Neonatal Ed. 2009 Mar;94(2):F87–91.
  • Harling AE, Beresford MW, Vince GS, Bates M, Yoxall CW. Does the use of 50% oxygen at birth in preterm infants reduce lung injury? Arch Dis Child Fetal Neonatal Ed. 2005 Sep;90(5):F401–5.
  • Kapadia VS, Chalak LF, Sparks JE, Allen JR, Savani RC, Wyckoff MH. Resuscitation of preterm neonates with limited versus high oxygen strategy. Pediatrics. 2013 Dec;132(6):e1488–96.
  • Kapadia VS, Lal CV, Kakkilaya V, Heyne R, Savani RC, Wyckoff MH. Impact of the Neonatal Resuscitation Program-Recommended Low Oxygen Strategy on Outcomes of Infants Born Preterm. J Pediatr. 2017 Dec;191:35–41.
  • Lundstrøm KE, Pryds O, Greisen G. Oxygen at birth and prolonged cerebral vasoconstriction in preterm infants. Arch Dis Child Fetal Neonatal Ed. 1995 Sep;73(2):F81–6.
  • Oei JL, Saugstad OD, Lui K, Wright IM, Smyth JP, Craven P, et al. Targeted Oxygen in the Resuscitation of Preterm Infants, a Randomized Clinical Trial. Pediatrics. 2017 Jan;139(1).
  • Rabi Y, Singhal N, Nettel-Aguirre A. Room-air versus oxygen administration for resuscitation of preterm infants: the ROAR study. Pediatrics. 2011 Aug;128(2):e374–81.
  • Rabi Y, Lodha A, Soraisham A, Singhal N, Barrington K, Shah PS. Outcomes of preterm infants following the introduction of room air resuscitation. Resuscitation. 2015 Nov;96:252–9.
  • Rook D, Schierbeek H, Vento M, Vlaardingerbroek H, van der Eijk AC, Longini M, et al. Resuscitation of preterm infants with different inspired oxygen fractions. J Pediatr. 2014 Jun;164(6):1322–3.
  • Soraisham AS, Rabi Y, Shah PS, Singhal N, Synnes A, Yang J, et al. Neurodevelopmental outcomes of preterm infants resuscitated with different oxygen concentration at birth. J Perinatol. 2017 Oct;37(10):1141–7.
  • Thamrin V, Saugstad OD, Tarnow-Mordi W, Wang Y, Lui K, Wright I, et al. Preterm Infant Outcomes after Randomization to Initial Resuscitation with FiO2 0.21 or 1.0. J Pediatr. 2018;201:55-61 e51.
  • Vento M, Moro M, Escrig R, Arruza L, Villar G, Izquierdo I, et al. Preterm resuscitation with low oxygen causes less oxidative stress, inflammation, and chronic lung disease. Pediatrics. 2009 Sep;124(3):e439–49.
  • Wang CL, Anderson C, Leone TA, Rich W, Govindaswami B, Finer NN. Resuscitation of preterm neonates by using room air or 100% oxygen. Pediatrics. 2008 Jun;121(6):1083–9.
Neonatal life support
Airway and ventilation

Discussion

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ILCOR staff

(modified: )

I feel that this is a timely statement of accurate science and agree with the content and recommendations
Reply
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ILCOR staff

(modified: )

Agree.
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ILCOR staff

(modified: )

As a 20 year veteran of NICU resuscitation I agree with starting at a lower concentration (30%) and adjusting upward as needed per pulse ox or ABG. We have had excellent results with keeping our FIO2 low . Also with giving surfactant and extubating quickly we have been able to keep those levels low.
profile avatar
ILCOR staff

(modified: )

I agree
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ILCOR staff

(modified: )

Agree
Reply
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ILCOR staff

(modified: )

Agree with the findings of the study.
Reply
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ILCOR staff

(modified: )

At our setting we start with 100% if we are doing chest compressions, other then that we start at 21% and increase as needed based on the level of resuscitation as needed.
Reply
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ILCOR staff

(modified: )

Thank you for your comment. There is little evidence to support 100% even with compressions but there is consensus at present in the absence of that evidence.
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ILCOR staff

(modified: )

Throughout the analysis, the use of the phrase "no benefit or harm" leaves grammatical room for misinterpretation. Does this mean "no (benefit or harm)" - in other words, no difference? Or does it mean "(no benefit) or harm" - in other words, outcomes are the same or worse? Perhaps a more clear wording can be found. Otherwise, thank you for an exhaustive, comprehensive analysis of the available data.
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ILCOR staff

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Agree with the recommendations for resuscitating Premature infants less than 35 weeks to start with the lower concentration. FiO2
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ILCOR staff

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I agree with the data as it is presented here.
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ILCOR staff

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Dear Highly Respected All Committee members, Present resuscitation practices are OK for preterm babies who are mildly sick/ almost well babies. It is not acceptable in moderate to severely ill babies those are limp, moderate to severe respiratory distress and gasping for oxygen. They deserve fast track resuscitation that means use higher oxygen concentration, use Neo Puff/ PPV to make them better quickly and to achieve normal oxygen saturation ( 90-94% ) within 1 minute ( not 10 minutes ) and reduce the oxygen supply as soon as reaches normal oxygen saturation. In first 30 seconds, we can dry, stimulate, suction and give oxygen at the same time. Newborn babies brain needs 3-4 mL of oxygen per 100 g of brain tissues per minute ( Ex: 1 kg baby needs about 3-4 mL of oxygen per minute considering brain weighs 100 g that is 10% of body weight). Besides other organs need oxygen as well. Waiting, watching, and monitoring pulse oxymetry and keeping them blue for 10 minutes are simply harming newborn babies brain, destroying their future and at least putting children behind the class. Pulse oxymetry don't pick up normal saturation for couple of minutes for poor perfusion in sick babies. We must prevent brain damages by all means. Honestly I see billions of dollars future litigation in USA and other countries against our respected organization. Litigation already started by individual lawyers in USA against the institution and got millions of dollars in each cases. We must protect our organization as well as our children. They are the future. I hope that we take this matter very seriously. In USA, EX Fed chairman Dr. Greenspan said : " No institution is too big to fail ". It is my utmost request to all of you to make them better ASAP.
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ILCOR staff

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Thank you Debasis. I won't repeat my reply from your comment which was similar for term babies but the points remain pertinent.
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ILCOR staff

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Thank you Debasis. I won't repeat my reply from your comment which was similar for term babies but the points remain pertinent.
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ILCOR staff

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Continued research may help us in the future Agree with current recommendations
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ILCOR staff

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I agree with the content and recommendations as well.
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ILCOR staff

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I thank the team who tabulated this data...very compelling to begin with lower FiO2 and adjust per the patients needs...with the appropriate monitors
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ILCOR staff

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I agree with the content and recommendations as well. We have experience in LIC and it is very compelling to begin with lower FiO2 and adjust for the patients needs...with the appropriate monitors. Need to change way of working following Science….and implement EBM approach EVERYWHERE!
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ILCOR staff

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We have been practicing this way for at least a couple of years. The data presented seems pretty consistent. Agree.
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ILCOR staff

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Until there is concrete, reliable data in the future to support using higher concentrations of O2 I think current recommendations are consistent with the information at hand and I agree with the recommendations
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ILCOR staff

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I always start with intermediate concentrations such as 30% oxygen. And I rarely need to use oxygen concentrations above 40%. And I can often reduce it by as much as 21%.
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ILCOR staff

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Overall conclusion is that there is no difference in major outcomes with using either lower or higher FiO2 in resuscitation. The corollary is, higher FiO2 is as safe and effective as lower. So why stress on lower FiO2? Hypoxia even if transient can cause further injury to premature brain, or to a compromised term brain which needs resuscitation. It can cause multiple organ damage and malfunction. Hypoxia is defined by decreased oxygen delivery to tissues and depends in a major way on hematocrit and tissue perfusion, even more than oxygen saturation and arterial partial pressure of O2. Maintaining intravascular volume may be as important as providing oxygen. Ideal oxygen saturation changes within minutes and hours after birth. The question is which one is more hazardous- hypoxia or hyperoxia. Multiple variables in this comparison matter, like, etiology, severity, extent, duration etc. There are so many varying situation and confounding variables in a case needing oxygen resuscitation that to make a blanket statement on FiO2 in this regard may not best serve the purpose. In fact this is what the conclusions here indicate. During resuscitation, each case should be evaluated on its own merits and best judgement be used towards establishing good oxygen delivery to tissues by providing adequate oxygen and optimizing intravascular volume without delay.
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ILCOR staff

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Thank you Rita as you raise excellent points. We had hoped that the Justification and Evidence to Decision section would explain some of your thinking and discussions in arriving at this CoSTR? You are completely correct that in the situation where no advantage is seen, the lower initial oxygen has been preferred because of concern about "possible" toxicity (although proven for 100% in term babies). However, the gaps and especially a lack of knowledge about: The optimum oxygen requirements for specific gestational age groups Appropriate oxygen targets for preterm infants How to best titrate oxygen in the delivery room for preterm infants Information regarding how cord clamping management impacts oxygen use following birth You are correct that guidelines guide and individual assessment is still needed. However our individualistic actions should be subsequently justified and researched.
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ILCOR staff

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Thank you Rita as you raise excellent points. We had hoped that the Justification and Evidence to Decision section would explain some of your thinking and discussions in arriving at this CoSTR? You are completely correct that in the situation where no advantage is seen, the lower initial oxygen has been preferred because of concern about "possible" toxicity (although proven for 100% in term babies). However, the gaps and especially a lack of knowledge about: The optimum oxygen requirements for specific gestational age groups Appropriate oxygen targets for preterm infants How to best titrate oxygen in the delivery room for preterm infants Information regarding how cord clamping management impacts oxygen use following birth You are correct that guidelines guide and individual assessment is still needed. However our individualistic actions should be subsequently justified and researched.
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ILCOR staff

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I agree with the analysis, but have some concern about the conclusion. An initial FiO2 of 21 to 30% may not be the safest option based on the published data so far. I know of 14 published RCTs of 'low' versus 'high' initial FiO2 for preterm resuscitation and these have been subjected (in various combinations) to at least 7 Systematic reviews. There is no convincing evidence of benefit or harm from either strategy. The data relating to term babies and short term measurement of oxidative stress are cause for concern in relation to high oxygen strategies however. Conversely, a report from the Canadian Neonatal Network (Rabi et al - Resuscitation et al 2015) on a very large preterm cohort, reported an increased rate of death or neurological injury following introduction of a policy to use air as an initial resuscitation gas. The use of 'some' oxygen appears to be sensible. The Torpido trial (Oei - Pediatrics 2017) very helpfully reported FiO2 during preterm resuscitation starting initially with 100% or air and subsequently adjusted by pulse oximetry to achieve an SpO2 of 80 to 95% by 5 minutes. It appears form their data (Figure 4 in the original paper) that an FiO2 of 40% was required by the majority. This paper also reported that failure to achieve the SpO2 target by 5 minutes of age was independently associated with mortality (although it is not clear whether this was a consequence of treatment or an index of initial illness severity) and also, in a non-pre-specified analysis, found an increase mortality rate at <28 weeks when resuscitation was started in air compared to starting in 100% oxygen. Given all of that, we have decided locally that starting preterm resuscitation with "some oxygen" means starting with 40% and titrating subsequently using pulse oximetry. Further studies required!
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ILCOR staff

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Thanks Bill. Of course the Torpido trial was one of the prompts for this review as it was already changing practice. However, that trial was almost fatally flawed in recruiting so few of the potential candidates, failing to complete because of lack of equipoise and the fact that, as you mention, the relevant analysis was not pre-specified. In fact the authors did not feel that the study should change practice. We are therefore left with RCT evidence vs observational evidence. There is clearly, as acknowledged, a lot more research needed to cover all of the questions raised. Some oxygen may well be sensible but unfortunately the evidence available makes it very difficult to stipulate more than the document has. Your local decison to implement 40% as an initial concentration may well help if observational data can be produced to to inform future studies. As you say they are needed but have to be able to recruit and complete. (This is in no way to criticise the Torpido Group whose study was supported by many)
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ILCOR staff

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I agree starting at a lower concentration (30%) and adjusting upward as needed per pulse oxymetry or HR monitors. Many times all we need to do is support them with pression, CPAP, more than higher FiO2; other times we must increase FiO2 to adjust the patients needs
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ILCOR staff

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The extensive studies and findings are commendable. Looking for answers via evidenced-based practice continues to be the driving force behind finding the answers posted for FIO2 needs for preterm infants, sick infants, etc. and the numerous possible sequelae that can affect them. In our institution, we start off with lowest O2 concentration and increase it based on pre-ductal SpO2 target.
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ILCOR staff

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I agree with the recomandation starting with lower concentration FiO2 and modulating FiO2 if you need to.
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ILCOR staff

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I agree, too often I see neonatologists starting resuscitation with High oxigen concentration without keeping in mind that in the first minutes of life a newborn CAN'T have 100% saturation!
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ILCOR staff

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I am agree with the commentaries abovebegin with lower FiO2 and adjust per the patients need.
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ILCOR staff

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Thank you so much for all the information. It sure makes it easier to start with lower concentrations of O2 in smaller babies.
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ILCOR staff

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We are currently beginning with lower Oxygen for all deliveries and following oxygen saturation’s per NRP recommendations. If an infant requires full resuscitation, we will increase oxygen to 100%.
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ILCOR staff

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I agree with the recommendations. All infant resuscitations should start at 21% and titrate up as required.
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ILCOR staff

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I completely agree with the statement issued
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ILCOR staff

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Iniciar sempre com FiO2 de 21%
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ILCOR staff

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I congratulate authors for their well done job. However, I want to signal that Rabi et al. "observed a higher risk of severe neurologic injury or death among preterm infants of ≤ 27 weeks gestation following a change in practice to initiating resuscitation with either room air or an intermediate oxygen concentration." (Resuscitation, 2015). Similarly, Oei et al. found that "Using RA to initiate resuscitation was associated with an increased risk of death in infants <28 weeks' gestation", although "This study was not a prespecified analysis, and it was underpowered to address this post hoc hypothesis reliably.". Therefore, it might be better to start resuscitation with some oxygen (FiO2 30-40%) adjusting it on the basis of SpO2.
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ILCOR staff

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I agree
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ILCOR staff

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I agree
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ILCOR staff

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Very well written and comprehensive review - BRAVO authors We start with oxygen through an oxygen concentrator (Sub Sahara Africa) in many unwell babies born early - with 100 deliveries per day we have many resus/day. Debasis Kanjilal 2019.01.18 10:19:38 (modified: 2019.01.18 17:57:45) Makes some good points especially valuable in our clinical setting. Some research in this space is needed. We have some very good outcomes despite lack of resources and medication like surfactant. Conversely poor outcomes. If we are giving compressions (often) we transfer when stable to Unit where we have CPAP and oxygen low flow. Its compelling research to start low and nitrate up - and guidelines of NRP; if full resus 100% oxygen
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ILCOR staff

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I agree with your well researched conclusions. Locally we have been using 40% start and reduced to 30% 2 years ago. Your recommended range of 21% to 30% could be interpreted as 21% or 30% . I would favour the latter as this seems to offer good transition in practice. One practical problem with starting in air is that people 'forget' to turn it up in a crisis, or turn up in very small increments, once they get distracted by intubation, CPR etc, whereas when the saturations are too high people usually notice and turn it down. So would pragmatically agree with the principle Start lower rather than start higher, but might still recommend 30% rather than air. I agree with others that once starting CPR should consider 100% oxygen.
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ILCOR staff

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Congrats to authors on the comprehensive job done, however the jury is still out. We are still in need of more compelling evidence to rescue ELGANs in 21% FiO2. While the partial pressure of oxygen in utero is quite low, and therefore brain is likely not significantly damaged from brief episode of hypoxia at birth, it has not yet been proven by any of the studies sited here. I agree that without compelling evidence some O2 (30-40%) would be best in this vulnerable group, at least until better long-term neurodevelopmental follow-up can be evaluated. First, do no harm.
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ILCOR staff

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I agree with the recommendations. I especially like the statement: "In still suggesting to start with low oxygen concentrations, we place value on avoiding exposure of preterm babies to additional oxygen without proven benefit for critical or important outcomes, as we are cognizant of harms in preterm animals and increased neonatal mortality in term infants exposed to high initial O2 concentration."
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ILCOR staff

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Thank you for the review. I agree with the recommendations.
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ILCOR staff

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Thanks to the authors of this well-written statement. 1) Presumably the format for presentation of results has been mandated, but strictly speaking the evidence is "inconclusive"; evidence that shows "no benefit or harm" is something different. 2) I agree that in the absence of evidence it is not possible to say if starting in air is better or worse than 30-40% but I am sympathetic to the concerns expressed above about use of air. I wonder if the second paragraph of the justification could be expanded to say something like "until further evidence is available, we recommend that individual units decide on a starting concentration between 21-30% based on local practice considerations and ongoing audit of care". 3) Second point in knowledge gaps: "Further evidence is needed from randomized studies about long term NDI outcomes".
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ILCOR staff

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Thank you for this excellent summary. Please consider creating from these recommendation, specific charts for birthing units that detail the oxygen saturation goals, according to gestation and minutes of life. These specifics are very useful to clinicians who may have limited education or excess care burdens, such as the night shift. Providers will 'do' if they 'know', and one wall chart to follow with room air progression to higher concentrations based on the oxygen saturation measures (oximetry) would be a clinical help. Ideally oximetry should be available, but this is not the case in many very busy obstetric and neonatal units in the global south. Clinical perfusion, including capillary refill and basics might be addressed please for those of us who are teaching in low-resource settings. We all, including me, benefit from simple, effective graphics right on the wall beside the resuscitation table when there is a stressful resuscitation or a sick baby, with limited help for these emergencies. Thank you for this comprehensive work.
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ILCOR staff

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Thank you for this excellent summary. Pending further RCTs dedicated to the administration of oxygen in ELGAN, we report the highest neurological and / or death risk reported by some studies (Rabi 2015; Oei 2016) on this fragile population resuscitated in the air or with low concentrations of oxygen. I think the most balanced choice is to start with 30% and continue on the basis of the levels of SaO2 in relation to the minutes of life.
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ILCOR staff

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I agree
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ILCOR staff

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I think that these recommendations are a good start to resuscitation guidelines for premature babies. However, ELBW 23 weekers should not be included with AGA 34 weekers in an all-encompassing statement. This is too wide of an age range, and the ELBW infants are more susceptible to complications from resuscitation. We have instituted a small-baby protocol for infants less than or equal to 30 weeks to prevent IVH in those infants, which involves more interventions than just oxygen titration. I would like to see research more specific to smaller age ranges in the premature infant population. I agree that starting with low O2 concentrations (30-40%) is better and increasing concentration as needed based on O2 saturations and age of life.
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ILCOR staff

(modified: )

Thank you for the review. I agree with the recommendations. I especially like the statement: "In still suggesting to start with low oxygen concentrations, we place value on avoiding exposure of preterm babies to additional oxygen without proven benefit for critical or important outcomes We are currently beginning with lower Oxygen for all deliveries and following oxygen saturation’s per NRP recommendations. If an infant requires full resuscitation, we will increase oxygen to 100%.
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ILCOR staff

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I agree with starting at a lower concentration (30%) and adjusting upward as needed per pulse ox or ABG. We have had excellent results with keeping our FIO2 low . Also with giving surfactant and extubating quickly we have been able to keep those levels low.
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ILCOR staff

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Thank you for the distinct Review. I agree with the recommendations. Nevertheless, it is somehow disappointing how uncertain we still are on that topic (in regard to quality of evidence).
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ILCOR staff

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Interesting to note that review consensus on science, showed ‘no benefit or harm’ on such significant wide range of Fio2 (most of these are downgraded for risk of bias and imprecision!!!) except in the critical outcome of all cause long-term mortality (1-3 years), that too from observational cohort studies with ≤28 weeks gestation receiving respiratory support at birth showed benefit of lower initial oxygen concentration compared to higher initial oxygen concentration. Wonder if it makes difference, assuming that there was NO uniformity of type of oxygen blenders usage, type of ventilators (invasive and noninvasive), type of oxygen saturation monitor usages and type of disease treated in premature infants? Does it make difference in the 'no benefit or harm' outcomes? Also, curious to know, the composition of air as we know consist of 78% N/21% Ox2/ 1% Argon and 0.04% Co2; Argon is supposed to be asphyxiant. And so just curious and wonder mixing of air and oxygen with Argon will have any effect in preterm infants lungs and brain? Inhalation of argon/oxygen mixtures have been used in adult humans to measure coronary and cerebral blood flow. Argons beneficial neuroprotective and organ protective properties have been observed in animal experiments in vitro and in vivo, but rarely in human studies. Another question I have is in preterm infants, the mitochondrial bioenergetic dysfunction is a fundamental mechanism of organs failure in premature infants. And we know oxygen used in mitochondria to generate ATP during oxidative phosphorylation. Do we need more and better understanding of this 'Oxygen Molecule’? Wonder in the meantime, it may be better not to give too much or too little for NOW?
Andrea Lube
(5 posts)

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I agree. We are following the recommendations with great results in the delivery room. We have serious problems in the transport, because we have great difficulties in providing compressed air for use in the transport.
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ILCOR staff

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"My humble request to you all: Report from 195 countries suggest children are suffering from hypoxia during birth and suffering from brain damages and exponential rise of Autism PLEASE SAVE THE CHILDREN IN THIS WORLD NOW AND MAKE A BETTER WORLD FOR TOMORROW . NEWBORN BLUE BABIES HAVE BEEN SUFFERING FROM HYPOXIA ( LOW OXYGEN ) INJURIES TO THEIR BRAIN, BEGAN IN 2006 AND MUST END NOW. THE TIME HAS COME TO CHANGE THE NRP/ILCOR/ANZCOR/ EUROPEAN NEWBORN RESUSCITATION COMMITTEES GUIDELINES IMMEDIATELY # REPORT FROM 195 COUNTRIES ( FROM 1990 TO 2015 ) ; GLOBAL BURDEN OF DISEASES ( GBD ) AND DEATHS FROM PRETERM BIRTH COMPLICATIONS, LOWER RESPIRATORY INFECTIONS, BIRTH ASPHYXIA, TRAUMA, CANCERS AND EXPONENTIAL RISE OF AUTISM. 90% newborn babies are pink within 1 minute. Why remaining 10% will suffer ? We are supposed to help them in the delivery room. Premature babies brain are more vulnerable than that of full term. We should all together help these children by all means and end their suffering. THIS IS UTMOST REQUEST TO YOU ALL. Parents are stressed out, they are not aware, no consent is obtained that their blue babies will remain blue over 10 minutes after birth. PLEASE HELP THEM. # Care for Autism and Other Disabilities — A Future in Jeopardy ( USA ) http://jamanetwork.com/journals/jamapediatrics/fullarticle/2613463?utm_medium=alert&utm_source=JAMA%20PediatrPublishAheadofPrint&utm_campaign=03-04-2017 http://jamanetwork.com/journals/jamapediatrics/fullarticle/2613461?utm_medium=alert&utm_source=JAMA%20PediatrPublishAheadofPrint&utm_campaign=03-04-2017 http://www.nejm.org/doi/full/10.1056/NEJMp1700697?query=pediatrics"
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ILCOR staff

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Would like to reiterate the same fact that in a resource constraint setting, a guideline should be feasible to use. After having attended many preterm deliveries and also as a national NRP faculty my opinion is skewed towards using room air for resuscitation of a preemie as well. Targeted Pre ductal sat may not be feasible in many of the delivery room settings and most of the settings don't have a blender to deliver required FiO2. In those cases, chances of harm is a real possibility with using 100% oxygen in preemies. There needs to be a clear cut guideline for these scenarios. Room air ventilation works well with either an AMBU bag or a T piece RESUSCITATOR (if available).
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ILCOR staff

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This is an excellent review that really encapsulates the available evidence in premature infants. I especially appreciate the clear discussion of the findings and the explicit recognition of the meaning of "neither harm nor benefit". The authors then make clear the basis for their recommendations, and finish by explicitly recognizing the limitations in the evidence base. Thank you.
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