Editorial
Oxygen supplementation in neonatal resuscitation
Suplementación de oxígeno en la reanimación neonatal
Máximo Vento
Servicio de Neonatología e Instituto de Investigación Sanitaria, Hospital Universitario y Politécnico La Fe, Valencia, Spain
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During embryogenesis, oxygen saturation (SatO<span class="elsevierStyleInf">2</span>) ranges from 15% to 20%, and in foetogenesis it increases to 45–55%. Hypoxaemia stimulates angiogenesis through direct activation of hypoxia-inducible factor alpha (HIFα) and indirectly through vascular endothelial growth factors (VEGFs) involved in vascular and tissue development. Thus, hypoxaemia is an essential morphogen for development during foetal life. Preterm birth alters this delicate regulatory mechanism and the development and differentiation of tissues overall, but especially in the lung, intestine, retina and central nervous system.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Current recommendations for postnatal stabilisation</span><p id="par0010" class="elsevierStylePara elsevierViewall">The onset of ventilation involves an abrupt increase in oxygen availability in the neonatal system associated with a physiological oxidative stress response that activates the enzymatic systems needed for postnatal adaptation. However, preterm newborns often require active resuscitation interventions, including oxygen supplementation. Excessive oxygen delivery may lead to hyperoxia associated with oxidative stress, while insufficient delivery may result in cardiac, haemodynamic and neurologic disturbances.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The 2015 guidelines of the International Liaison Committee on Resuscitation (ILCOR) recommend the use of room air for the resuscitation of full-term newborns, maintaining the recommendations of the ILCOR 2010 guidelines. When it comes to preterm newborns less than 35 weeks’ gestational age, they recommend the use of initial fractions of inspired oxygen (iFiO<span class="elsevierStyleInf">2</span>) between 0.21 and 0.3, to be titrated in each individual based on the changes in saturation with the goal of achieving the preductal SpO<span class="elsevierStyleInf">2</span> ranges found in the assessment of newborns delivered vaginally at term and at sea level. The 2015 ILCOR guidelines do not recommend initiating stabilisation with an iFiO<span class="elsevierStyleInf">2</span> greater than 0.65 under any circumstances<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). The impact of this recommendation is unknown, and this is acknowledged as one of the most relevant knowledge gaps in modern neonatology considering that there are 15 million preterm births a year and more than 50% of these newborns receive oxygen supplementation.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Initial fraction of inspired oxygen (iFiO<span class="elsevierStyleInf">2</span>) in the stabilisation of preterm newborns</span><p id="par0020" class="elsevierStylePara elsevierViewall">The most recent evidence available puts into question the management of oxygen supplementation in the delivery recommended by the 2015 ILCOR guidelines. A systematic review from 2016 analysed the most relevant clinical outcomes—including death, bronchopulmonary dysplasia and intraventricular haemorrhage—in eight randomised controlled trials published to date that included infants born before 29 weeks’ gestation and compared stabilisation with iFiO<span class="elsevierStyleInf">2</span> of 0.3 or lower (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>251) and iFiO<span class="elsevierStyleInf">2</span> of 0.6 or greater (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>258).<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> The study did not find differences between the two groups for the primary outcome, which was death before hospital discharge. However, when the analysis was restricted to trials that were masked for FiO<span class="elsevierStyleInf">2</span> manipulation, mortality was lower in the group with iFiO<span class="elsevierStyleInf">2</span> of 0.3 or lower (relative risk [RR], 0.46; 95% confidence interval [CI], 0.23–0.92). Conversely, when the analysis was restricted to unmasked trials, the results supported the use of iFiO<span class="elsevierStyleInf">2</span> of 0.6 or greater (RR, 1.94; 95% CI, 1.02–3.68). The unmasked trials included the TO2RPIDO 1 study, which compared resuscitation with iFiO<span class="elsevierStyleInf">2</span> of 0.21 versus 1.0. This study showed a significantly higher mortality in infants born before 29 weeks’ gestation resuscitated with an iFiO<span class="elsevierStyleInf">2</span> of 0.21 (18.9%) compared to those resuscitated with an iFiO<span class="elsevierStyleInf">2</span> of 1.0 (5.9%). The number of patients recruited in this study was notably greater than in other studies, so this study had a compelling weight in the final results of the statistical analysis.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">3</span></a> Recently, the Canadian Neonatal Network published a retrospective cohort study comparing mortality in preterm infants born at 27 or fewer weeks’ gestation before and after 2006, when the resuscitation protocols in the delivery room were modified and the use of iFiO<span class="elsevierStyleInf">2</span> was generally changed from 1.0 to .21. The adjusted odds ratio for the primary outcome of death or severe neurological impairment was significantly higher for the group with room air resuscitation (AOR, 1.36; 95% CI, 1.11–1.66).<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Interpreting these results poses serious difficulties, as the studies had very different designs and were conducted over an extended period of time. Thus, in studies conducted more recently, researchers were familiar with the practice of oxygen supplementation guided by pulse oximetry, used target saturations derived from studies in well-adapted patients and had experience in the customised titration of FiO<span class="elsevierStyleInf">2</span>. Conversely, researchers in earlier studies lacked this information and still faced a learning curve. Another possible explanation would be a type 1 error, considering the weak statistical significance of the outcome differences between the masked and the unmasked studies.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Target saturations in the delivery room</span><p id="par0030" class="elsevierStylePara elsevierViewall">No data are available to assess whether adherence to the target saturations proposed by the ILCOR are associated with improvements in mortality and morbidity. This is another knowledge gap that requires exhaustive investigation in upcoming years. A study presented recently at the 2016 European Association for Paediatric Research (EAPS) Congress summarised the clinical outcomes (morbidity and mortality) of reaching or failing to reach target saturations in preterm infants by the minute-to-minute analysis of SatO<span class="elsevierStyleInf">2</span> and FiO<span class="elsevierStyleInf">2</span> in 706 patients included in eight randomised trials that compared resuscitation with high versus low FiO<span class="elsevierStyleInf">2</span>.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> The primary clinical outcome was the correlation between SatO<span class="elsevierStyleInf">2</span> at 5<span class="elsevierStyleHsp" style=""></span>min and death and/or intraventricular haemorrhage (IVH) with a grade 3 or greater. Interestingly, only 23% of the patients achieved the expected target saturations (85% at 5<span class="elsevierStyleHsp" style=""></span>min), while 55% reached lower saturations and 22% amply overshot the target. The most relevant finding was that the patients that failed to reach the 85% target were more likely to die (OR, 1.5; 95% CI, 1.1–2.6) and/or to develop IVH (OR, 2.4; 95% CI, 1.2–4.2). The risk of both death and IVH increased with each additional minute that it took patients to reach the target saturation. We ought to highlight that increases in heart rate in these patients did not guarantee a favourable clinical outcome.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The analysis did not establish whether the higher frequency of poor outcomes in the patients that did not reach target saturations was due to insufficient oxygen supplementation or to underlying critical conditions that prevented these patients from achieving stability with the established interventions.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="par0040" class="elsevierStylePara elsevierViewall">Oxygen supplementation in extremely preterm newborns remains an uncharted territory. We have yet to determine the optimal initial FiO<span class="elsevierStyleInf">2</span>, the target saturations throughout stabilisation, and the air/oxygen mixer mode settings required to achieve adequate stabilisation. Until we obtain results from the large international studies that are currently underway, it may be convenient to initiate reanimation with higher FiO<span class="elsevierStyleInf">2</span> settings (0.4), or, if the patient does not respond adequately, to adjust flow more rapidly (intervals of 20–30% every 10–15<span class="elsevierStyleHsp" style=""></span>s) with the purpose of optimising cardiac output and achieving haemodynamic stability. Perhaps the failure to achieve established SatO<span class="elsevierStyleInf">2</span> targets could serve as a clinical indicator for the identification of high-risk patients that require even more careful monitoring.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Funding</span><p id="par0045" class="elsevierStylePara elsevierViewall">The author has obtained support through the RETICS, with funding from the National Plan for R&D&I 2008–2011, the General Subdirectorate for the Evaluation and Promotion of Research of the Instituto de Salud Carlos III, and the European Regional Development Fund RD12/0026.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Oxygen in foetal life" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Current recommendations for postnatal stabilisation" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Initial fraction of inspired oxygen (iFiO) in the stabilisation of preterm newborns" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "Target saturations in the delivery room" ] 4 => array:2 [ "identificador" => "sec0025" "titulo" => "Conclusions" ] 5 => array:2 [ "identificador" => "sec0030" "titulo" => "Funding" ] 6 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Vento M. Aporte de oxígeno en la reanimación neonatal. An Pediatr (Barc). 2017;86:1–3.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Time (min) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Target saturation (%) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60–65 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">65–70 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70–75 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">75–80 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">80–85 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">85–95 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1300487.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Target saturations during stabilisation expressed in minutes after birth recommended by the 2015 ILCOR guidelines.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a></p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Oxygen supplementation in the neonatal period: changing the paradigm" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M. Vento" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/000360646" "Revista" => array:6 [ "tituloSerie" => "Neonatology" "fecha" => "2014" "volumen" => "105" "paginaInicial" => "323" "paginaFinal" => "331" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24931324" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Part 13: neonatal resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.H. Wyckoff" 1 => "K. Aziz" 2 => "M.B. Escobedo" 3 => "V.S. Kapadia" 4 => "J. Kattwinkel" 5 => "J.M. 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Rich" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/archdischild-2016-310435" "Revista" => array:2 [ "tituloSerie" => "Arch Dis Child Fetal Neonatal Ed" "fecha" => "2016" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Outcomes of preterm infants following the introduction of room air resuscitation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Y. Rabi" 1 => "A. Lodha" 2 => "A. Soraisham" 3 => "N. Singhal" 4 => "K. Barrington" 5 => "P.S. Shah" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.resuscitation.2015.08.012" "Revista" => array:6 [ "tituloSerie" => "Resuscitation" "fecha" => "2015" "volumen" => "96" "paginaInicial" => "252" "paginaFinal" => "259" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26359156" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "EAPS-0378" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Outcomes of pulse oximetry targeting during delivery room stabilization of preterm infants" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Vento" 1 => "O.D. Saugstad" 2 => "I. Wright" 3 => "N. Finer" 4 => "W. Rich" 5 => "D. Rook" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "Eur J Pediatr" "fecha" => "2016" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23412879/0000008600000001/v1_201612270102/S234128791630148X/v1_201612270102/en/main.assets" "Apartado" => array:4 [ "identificador" => "25501" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Editorial" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/23412879/0000008600000001/v1_201612270102/S234128791630148X/v1_201612270102/en/main.pdf?idApp=UINPBA00005H&text.app=https://analesdepediatria.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S234128791630148X?idApp=UINPBA00005H" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 9 | 9 | 18 |
| 2024 October | 53 | 35 | 88 |
| 2024 September | 52 | 30 | 82 |
| 2024 August | 65 | 54 | 119 |
| 2024 July | 49 | 34 | 83 |
| 2024 June | 46 | 27 | 73 |
| 2024 May | 51 | 31 | 82 |
| 2024 April | 56 | 37 | 93 |
| 2024 March | 52 | 34 | 86 |
| 2024 February | 42 | 35 | 77 |
| 2024 January | 27 | 25 | 52 |
| 2023 December | 21 | 18 | 39 |
| 2023 November | 38 | 21 | 59 |
| 2023 October | 38 | 22 | 60 |
| 2023 September | 33 | 23 | 56 |
| 2023 August | 37 | 15 | 52 |
| 2023 July | 40 | 34 | 74 |
| 2023 June | 26 | 32 | 58 |
| 2023 May | 36 | 18 | 54 |
| 2023 April | 24 | 23 | 47 |
| 2023 March | 22 | 35 | 57 |
| 2023 February | 37 | 15 | 52 |
| 2023 January | 26 | 17 | 43 |
| 2022 December | 38 | 27 | 65 |
| 2022 November | 56 | 40 | 96 |
| 2022 October | 35 | 41 | 76 |
| 2022 September | 29 | 26 | 55 |
| 2022 August | 44 | 41 | 85 |
| 2022 July | 29 | 35 | 64 |
| 2022 June | 26 | 30 | 56 |
| 2022 May | 26 | 31 | 57 |
| 2022 April | 23 | 28 | 51 |
| 2022 March | 38 | 51 | 89 |
| 2022 February | 31 | 25 | 56 |
| 2022 January | 30 | 30 | 60 |
| 2021 December | 32 | 44 | 76 |
| 2021 November | 24 | 44 | 68 |
| 2021 October | 47 | 59 | 106 |
| 2021 September | 19 | 36 | 55 |
| 2021 August | 24 | 49 | 73 |
| 2021 July | 24 | 26 | 50 |
| 2021 June | 25 | 31 | 56 |
| 2021 May | 45 | 48 | 93 |
| 2021 April | 80 | 66 | 146 |
| 2021 March | 45 | 33 | 78 |
| 2021 February | 22 | 23 | 45 |
| 2021 January | 32 | 16 | 48 |
| 2020 December | 14 | 23 | 37 |
| 2020 November | 24 | 23 | 47 |
| 2020 October | 23 | 24 | 47 |
| 2020 September | 17 | 27 | 44 |
| 2020 August | 21 | 45 | 66 |
| 2020 July | 21 | 17 | 38 |
| 2020 June | 12 | 9 | 21 |
| 2020 May | 36 | 20 | 56 |
| 2020 April | 30 | 10 | 40 |
| 2020 March | 36 | 17 | 53 |
| 2020 February | 24 | 14 | 38 |
| 2020 January | 23 | 6 | 29 |
| 2019 December | 32 | 14 | 46 |
| 2019 November | 11 | 9 | 20 |
| 2019 October | 25 | 16 | 41 |
| 2019 September | 16 | 20 | 36 |
| 2019 August | 17 | 16 | 33 |
| 2019 July | 20 | 31 | 51 |
| 2019 June | 15 | 22 | 37 |
| 2019 May | 20 | 30 | 50 |
| 2019 April | 26 | 31 | 57 |
| 2019 March | 21 | 18 | 39 |
| 2019 February | 29 | 11 | 40 |
| 2019 January | 24 | 15 | 39 |
| 2018 December | 34 | 41 | 75 |
| 2018 November | 48 | 27 | 75 |
| 2018 October | 84 | 27 | 111 |
| 2018 September | 27 | 13 | 40 |
| 2018 August | 8 | 0 | 8 |
| 2018 July | 5 | 0 | 5 |
| 2018 June | 3 | 0 | 3 |
| 2018 May | 7 | 0 | 7 |
| 2018 April | 26 | 0 | 26 |
| 2018 March | 40 | 0 | 40 |
| 2018 February | 28 | 0 | 28 |
| 2018 January | 16 | 0 | 16 |
| 2017 December | 31 | 0 | 31 |
| 2017 November | 14 | 0 | 14 |
| 2017 October | 17 | 0 | 17 |
| 2017 September | 15 | 0 | 15 |
| 2017 August | 7 | 0 | 7 |
| 2017 July | 27 | 1 | 28 |
| 2017 June | 21 | 15 | 36 |
| 2017 May | 27 | 20 | 47 |
| 2017 April | 83 | 83 | 166 |
| 2017 March | 20 | 15 | 35 |
| 2017 February | 13 | 13 | 26 |
| 2017 January | 39 | 32 | 71 |
| 2016 December | 4 | 10 | 14 |
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