Initial Oxygen Concentration for Term Neonatal Resuscitation
Isayama T, Dawson JA, Roehr CC, Rabi Y, Weiner GM, Aziz K, Kapadia VS, de Almeida MF, Trevisanuto D, Mildenhall L, Liley HG, Hosono S, Kim HS, Szyld E, Perlman JM, Velaphi S, Guinsburg R, Welsford M, Nishiyama C, Wyllie JP and Wyckoff MH. Initial oxygen concentration for term neonatal resuscitation [Internet] Brussels, Belgium: International Liaison Committee on Resuscitation (ILCOR) Neonatal Life Support Task Force, November 12, 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 term 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.
Welsford M, Nishiyama C, Shortt C, Isayama T, Dawson JA, Weiner G, Roehr CC, 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.2018-1825
Initial Oxygen Concentration for Term Neonatal Resuscitation PICOST
The PICOST (Population, Intervention, Comparator, Outcome, Study Designs, and Time Frame)
Population: Newborn infants who receive respiratory support at birth (Term or Late preterm, ≥ 35 weeks gestation)
Intervention: Lower initial oxygen concentration
Comparison: Higher initial oxygen concentration
- All cause short-term mortality (in-hospital or 30 days)
- All cause long-term mortality (1-3 years)
- Long-term neurodevelopmental impairment(1-3 years)
- Hypoxic-ischemic encephalopathy (Sarnat Stage 2-3)
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 Excluded animal studies, unpublished studies (e.g., conference abstracts).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 (≥ 35 weeks, ≥37 weeks); grouped lower and higher oxygen concentrations; explicit oxygen saturation targeting vs no oxygen saturation targeting
PROSPERO Registration: CRD42018084902
Consensus on Science
For the critical outcome of all cause short-term mortality (in-hospital or 30 days), the evidence of low certainty (downgraded for risk of bias and imprecision) from 7 RCTs (and quasi RCTs) involving 1469 term and late preterm newborns (≥ 35 weeks gestation) receiving respiratory support at birth showed benefit of starting with 21% compared to 100% oxygen (RR=0.73 95% CI 0.57-0.94, I2=0%); 46/1000 fewer babies died when respiratory support at birth was started with 21% compared to 100% oxygen [95% CI: 73/1000 fewer to 10/1000 fewer] (Ramji 1993 809; Saugstad 1998 e1; Vento 2003 240; Ramji 2003 510; Bajaj 2005 206; Vento 2005 1393; Toma 2006 33).
For the critical outcome of all cause long-term mortality (1-3 years), no evidence was identified.
For the critical outcome of long-term neurodevelopmental impairment (NDI, 1-3 years) among survivors who were assessed, evidence of very low certainty (downgraded for risk of bias and imprecision) from 2 RCTs (and quasi RCTs) involving 360 term and late preterm newborns (≥ 35 weeks gestation) receiving respiratory support at birth showed no benefit or harm of starting with 21% compared to 100% oxygen (RR=1.41 95% CI 0.77-2.60, I2=0%); 36/1000 more babies with NDI when respiratory support at birth was started with 21% compared to 100% oxgyen [95% CI: 20/1000 fewer to 142/1000 more] (Saugstad 2003 e1; Bajaj 2005 206).
For the critical outcome of hypoxic-ischemic encephalopathy (Sarnat Stage 2-3) evidence of low certainty (downgraded for risk of bias and imprecision) from 5 RCTs (and quasi RCTs) involving 1359 term and late preterm newborns (≥ 35 weeks gestation) receiving respiratory support at delivery showed no benefit or harm of 21% compared to 100% oxygen (RR=0.90 95% CI 0.71-1.14, I2=8%); 20/1000 fewer babies with hypoxic-ischemic encephalopathy when respiratory support at birth was started with 21% compared to 100% oxygen [95% CI: 57/1000 fewer to 27/1000 more] (Ramji 1993 809; Saugstad 1998 e1; Ramji 2003 510; Bajaj 2005 206; Toma 2006 33).
No studies were identified that compared any intermediate oxygen concentrations.
For term and late preterm newborns (≥ 35 weeks gestation) receiving respiratory support at birth, we suggest starting with 21% oxygen (weak recommendation, low certainty evidence). We recommend against starting with 100% oxygen (strong recommendation, low certainty evidence).
Justification and Evidence to Decision Highlights
In making this recommendation, the Neonatal Life Support Task Force considered the following:
Parents and clinicians rate mortality as a critical outcome. Despite low certainty of the evidence, the large reduction in the primary outcome of short term mortality (NNT=22) with no demonstrated adverse effects favors use of 21% oxygen as the initial gas for resuscitation in term and late preterm newborns. Although there are no published cost data, it is likely that initiating resuscitation with 21% oxygen does not add cost and might result in cost savings compared to initial 100% oxygen in some settings. Babies born in low resource settings are disadvantaged by increased mortality and morbidity. Therefore, it is plausible that using 21% oxygen compared to 100% oxygen has greater impact in low resource settings. Use of 21% oxygen for initial resuscitation is universally feasible and is now accepted by the neonatal community world-wide.
- There were relatively few late preterm (35-36 week gestation) infants in the studies. The confidence in our recommendations for this gestational age group is low. More studies are needed regarding this population
- Does titration of oxygen to SpO2 targets impact conclusions?
- Need data comparing intermediate oxygen concentrations
- Does delayed cord clamping have any effect on the impact of oxygen exposure?
EtD table: Should Low FiO2 vs. High FiO2 be used for Term Neonatal Resuscitation?
- Bajaj N, Udani RH, Nanavati RN. Room air vs. 100 per cent oxygen for neonatal resuscitation: a controlled clinical trial. J Trop Pediatr. 2005;51(4):206–11.
- Ramji S, Ahuja S, Thirupuram S, Rootwelt T, Rooth G, Saugstad OD. Resuscitation of asphyxic newborn infants with room air or 100% oxygen. Pediatr Res. 1993;34(6):809–12.
- Ramji S, Rasaily R, Mishra PK, Narang A, Jayam S, Kapoor AN, et al. Resuscitation of asphyxiated newborns with room air or 100% oxygen at birth: a multicentric clinical trial.Indian Pediatr. 2003;40(6):510–7.
- Saugstad OD, Rootwelt T, Aalen O. Resuscitation of asphyxiated newborn infants with room air or oxygen: an international controlled trial: the Resair 2 study. Pediatrics. 1998;102(1):e1.
- Saugstad OD, Ramji S, Irani SF, El-Meneza S, Hernandez EA, Vento M, et al. Resuscitation of newborn infants with 21% or 100% oxygen: follow-up at 18 to 24 months. Pediatrics. 2003;112(2):296–300.
- Toma AI, Nanea M, Scheiner M, Mitu R, Petrescu I, Matu E. Effects of the gas used in the resuscitation of the newborn in the post-resuscitation haemodynamics. Asfixia Perinatala Primul Congres National de Neonatologie. 2006: 34–44.
- Vento M, Asensi M, Sastre J, Lloret A, Garcia-Sala F, Vina J. Oxidative stress in asphyxiated term infants resuscitated with 100% oxygen. J Pediatr. 2003;142(3):240–6.
- Vento M, Sastre J, Asensi MA, Vina J. Room-air resuscitation causes less damage to heart and kidney than 100% oxygen. Am J Respir Crit Care Med. 2005;172(11):1393–8.