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NLS 5325 Strategies for Positive Pressure Ventilation: TF Scoping Review

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Conflict of Interest Declaration

The ILCOR Continuous Evidence Evaluation process is guided by a rigorous ILCOR Conflict of Interest policy. The following Task Force members and other authors were recused from the discussion as they declared a conflict of interest:

The following Task Force members and other authors declared an intellectual conflict of interest and this was acknowledged and managed by the Task Force Chairs and Conflict of Interest committees:

Author Madar is author of guidelines cited in the review. {Madar 2021 326}

Author Schmölzer is author of several studies included, or cited in the review but was excluded from decisions about inclusion of these studies. {Espinoza 2019 F98, Fuerch 2022 100327, Hooper 2013 e70895, Kaufman 2013 F410, Kirpalani 2019 1175, Klingenberg 2013 F222, Mian 2019 F57, Ngan 2017 F525, Schmölzer 2015 844, Schmölzer 2010 F393, Schmölzer 2012 377}. Author Schmölzer is author of neonatal resuscitation guidelines cited in the review {Aziz 2021 e2020038505E, Lee 2025 S385, Wyckoff 2020 S185}

Author Hooper is author of several studies included in the review, and was excluded from decisions about inclusion of these studies. {Ersdal 2020 78, Hooper 2013 e70895, Hooper 2013 , Klingenberg 2013 F222, Kuypers 2025 728, Kuypers 2020 , Probyn 2005 1764, Pryor 2020 891, Schilleman 2013 457, Schmölzer 2015 844, Schmölzer 2012 377, van Vonderen 2015 F514}

Author te Pas is author several studies cited in the review and was excluded from decision about inclusion of these studies. {Cavigioli 2023 555, Hooper 2013 e70895, Hooper 2013 , Kuypers 2025 728, Kuypers 2020 , Pryor 2020 891, Schilleman 2013 457, te Pas 2009 369, van Vonderen 2015 F514, Yang 2020 605}

Author Kamlin is author of several studies cited in the review and was excluded from decisions about inclusion of these studies. {Kaufman 2013 F410, Schmölzer 2015 844, Schmölzer 2010 F393, Schmölzer 2012 377, te Pas 2009 369}

Author Kawakami has no conflict of interest

Author Ersdal is author of guidelines and several studies cited in the review and was excluded from decisions about inclusion of these studies. {Bjorland 2022 222, Ersdal 2020 78, Holte 2021 128, Holte 2019 e000544, Kibsgaard 2023 705, Linde 2018 1, Linde 2017 80, Madar 2021 326}

Task Force Synthesis Citation

Insert citation for ILCOR.org posting of a Task Force Synthesis of a Scoping Review

Example – Note: this should reflect the TF members who contributed to the Synthesis not an author list of the Scoping review

Madar J, Schmölzer GM, Hooper SB, Te Pas AB, Kamlin O, Kawakami MD, Ersdal H, Rabi Y, Weiner G, Liley HG on behalf of the Life Support Task Force. 

Strategies for positive pressure ventilation immediately after birth to improve outcomes: A scoping review [Internet] Brussels, Belgium: International Liaison Committee on Resuscitation (ILCOR) Neonatal Life Support Task Force, 2025.  Available from: http://ilcor.org

Methodology

For newborn infants who do not establish effective spontaneous breathing after birth, positive pressure ventilation (PPV) is required to achieve lung aeration and gas exchange. In most cases, PPV will reverse hypoxic bradycardia and reduce the need for other circulatory interventions such as chest compressions. Levels for variables including the starting peak inflation pressure (PIP) and positive end-expiratory pressure (PEEP), inspiratory time, and ventilation rate are recommended in clinical practice guidelines, which are mainly based on clinical experience and consensus. This scoping review aimed to review the current evidence to determine if there are sufficient grounds to prompt changes to current approaches.

The most recent review assessing PPV at birth was in 2010 {Perlman 2010 S516} updating recommendations made in 2005 {2006 e955} on ‘initial breaths’ for term and preterm infants. These reviews were made prior to the adoption of contemporary methods of systematic review including GRADE methodology by ILCOR. {Guyatt 2008 924}

When an infant is apnoeic or has insufficient respiratory effort after birth, the intention of the first, or initial phase of PPV is to promote liquid clearance from the airways and the entry of air into the alveoli to establish a functional residual capacity (FRC). This process is critical for the onset of pulmonary gas exchange and stimulates a rapid and large decrease in pulmonary vascular resistance that increases pulmonary blood flow and supports cardiac output. {Hooper 2018 187} FRC is the volume of gas retained in the lung at end-expiration and is determined by a balance between the elastic outward recoil of the chest wall (promoting lung expansion) and inward elastic recoil of lung tissue. When it is optimized, the work of breathing, (or need for positive pressure for inflation) is minimized. However, the FRC is not a fixed number, but is influenced by gestation, size, posture, activity, and other variables. In newborns, values of 15-30 mL/kg are often estimated to be sufficient.   

The goals of subsequent PPV are to maintain FRC and to achieve gas exchange sufficient for normal bodily function. At the beginning of this second phase, liquid that accumulated in interstitial lung tissue during lung aeration causes pulmonary oedema. {Hooper 2016 F266} This is usually mild but can be severe if large volumes of airway liquid were cleared via this route; this liquid is gradually (over 4-6 hours) cleared from lung tissue via lymphatics and vasculature. {Miserocchi 1990 2168} Lung mechanics markedly differ between these first two phases and the transition between them is typically gradual, not abrupt. The duration of the initial phase may vary depending on the extent of any underlying lung pathology, PPV variables such as inflation pressures, end expiratory pressure and inspiratory times, as well as the infant’s own respiratory effort, if present. Whether the goal should be rapid or more gradual completion of the initial phase is uncertain. {Tingay 2019 608} Lung volume measurements or imaging techniques (not usually accessible at the point of care) are needed for accurate determination of the boundary between initial and subsequent phases. In most resuscitation events, clinical judgements are made as to the time of transition between phases, but if available, respiratory function monitoring devices and lung ultrasound can assist. 

It is important in both phases to avoid over-distension of the lung, which can cause lung injury, but prolonged or recurrent atelectasis will impair gas exchange. 

Initial PIP of 20-25 cmH2O for preterm infants and 30-40 cmH2O for term infants were suggested as adequate. These recommendations were largely based on historical observational data in limited populations of usually intubated asphyxiated newborns. {Boon 1979 1031, Hird 1991 69, Hull 1969 58, Lindner 1999 961, Milner 1984 1563, Palme-Kilander 1993 11, Vyas 1981 635} There was insufficient evidence identified to recommend either initial or subsequent inflation times. Studies included inflations up to 20 seconds. {Lindner 1999 961} No recommendations were made on the ventilation rate or duration of PPV between interventions. No recommendations were made relating to other ventilatory parameters, including delivered tidal volume.

Subsequent ILCOR reviews have considered some aspects of PPV in term or preterm infants. In 2015 an ILCOR CoSTR on the delivery of PEEP suggested that a PEEP of 5 cmH2O has benefit for preterm infants, but no recommendations could be made for term infants because of a lack of evidence. {Wyckoff 2015 S543} Evidence updates in 2020 and 2025 identified no new information to change recommendations. {Liley 2025 , Wyckoff 2020 S185} In 2022 an ILCOR systematic review found insufficient evidence to make a recommendation for or against the use of respiratory function monitoring in newborn infants receiving respiratory support at birth. Several infant outcomes and resuscitation variables were specified as critical including tidal volumes within a target range of between 4-8 mL/kg. {Fuerch 2022 100327} An ILCOR systematic review of trials examining initial sustained inflations focused on inflations longer than 1 second but only found RCTs examining inflations longer than 5 seconds, and recommended against these based on available evidence. A more recent evidence update found insufficient evidence to change this recommendation. {Kapadia 2021 e2020021204, Liley 2025 }

Acknowledging that lung mechanics are changing over time and that there is no clear relationship between volume delivered and pressures used, the optimal inflation times (<5 seconds) and the need for initial recruitment inflations remain uncertain. As a result, there is also variation in recommendations on ventilatory rate and inflation time for PPV and length of time of PPV delivery between decisions about interventions. These are areas where ILCOR has not made any previous recommendation and where differences are evident in the approach recommended by different associatations – for example – the European Resuscitation Council (ERC) {Hogeveen 2025 110766} and the American Heart Association (AHA). {Lee 2025 S385}

This scoping review reviewed the evidence supporting strategies of PPV at birth. It attempted to address the following questions:

For PPV delivered to a newborn infant immediately after birth by any device

1. What are the optimum initial PIP settings?

2. What is the optimum initial inflation time?

3. What is the optimum ventilation rate?

4. What is the optimum duration of PPV delivered between reassessment/interventions?

5. If measured, what are the optimum target tidal volumes to aim for?

6. For infants making respiratory effort, is synchronized PPV superior to non-synchronized PPV?

7. What are (is it possible to define) the optimum strategies to adopt in adjusting PPV after initial delivery of inflations?

8. Is it possible to determine whether any current guideline recommendations confer advantage over any other?

This scoping review did not attempt to re-examine in detail areas already addressed by other ILCOR systematic reviews, including superiority/inferiority of devices (T-piece vs self inflating bag (SIB) vs flow inflating bag (FIB) vs ventilator), PEEP vs no PEEP for respiratory support or sustained inflation greater than 5 seconds.

The interrelated nature of the interventions meant that it was difficult to define a single PICOST encompassing all variables. Several PICOSTs were developed which reflected different elements of any PPV strategy but where search strategies and previous recommendations overlapped. However, it is important to recognize that while PPV parameters have been assessed in isolation, as some of the parameters are closely interrelated, changing one can affect the efficacy of another. All PICOST’s had a common set of outcomes, study design and timeframe.

Scoping Review

Webmaster to insert the Scoping Review citation and link to Pubmed using this format when/if it is available.

Example: Note: This should reflect the Scoping Review Contributing Authors

Usman M, Fitzpatrick-Lewis D, Kenny M, Parminder R, Atkins DL, Soar J, Nolan J, Ristagno G, Sherifali D Effectiveness of antiarrhythmic drugs for shockable cardiac arrest: A systematic review Resuscitation 132:November 2018 63-72 PMID:30179691 DOI:10.1016/j.resuscitation.2018.08.025

PICOST (Outcomes, Study Designs and Time Frame are similar and outlined below)

5325a – Peak Inflation Pressure

Population Newborn infants who receive PPV immediately after birth

Intervention Higher or lower initial peak inflation pressure (PIP)

Comparisons Specified initial PIP

5325b – Inflation time

Population Newborn infants who receive PPV immediately after birth

Intervention longer or shorter initial inflation time

Comparisons Specified initial inspiratory time.

5325c – Inflation Rate

Population Newborn infants who receive PPV immediately after birth

Intervention Higher or lower initial ventilation rate

Comparisons Specified initial ventilation rate

5325d – Duration of PPV

Population Newborn infants who receive PPV immediately after birth

Intervention Higher or lower duration of PPV

Comparison Specified Initial duration of PPV

5325e –Exhaled Tidal Volume

Population Newborn infants who receive PPV immediately after birth

Intervention Higher or lower targeted exhaled tidal volumes (VTe)

Comparison Initial targeted VTe

5325f - Synchrony

Population Newborn infants who receive PPV immediately after birth

Intervention Synchronized PPV

Comparison Non-synchronized PPV

5325g – Adjustment

Population Newborn infants who receive PPV immediately after birth

Intervention Alternative method of adjusting/optimizing PPV

Comparison Initial method of adjusting/optimizing PPV

5325h – Guideline recommendations (as a ‘bundle’ of interventions)

Population Newborn infants who receive PPV immediately after birth

Intervention Any other guideline approach on delivery of PPV

Comparison Reference guideline approach

Outcomes

The outcomes assessed in this scoping review included those proposed by the Neonatal Utstein framework {Foglia 2023 e2022059631} and other outcomes included by Task Force consensus. {Strand 2020 328}

Primary outcome

Success of resuscitation

  • Time until heart rate (HR) >100 beats per minute (bpm) after birth (Important)

Other outcomes

Success of resuscitation

  • Survival in the delivery room (Critical)
  • Receipt of chest compressions (Important)
  • Time to first breath (Important)
  • Receipt of intubation in the delivery room (Important)
  • Duration of positive pressure ventilation (Important)
  • Final oxygen concentration in the delivery room (Important)

Neonatal Morbidity

  • Intraventricular hemorrhage (Papile grade III or IV) {Papile 1978 } (Critical)
  • Bronchopulmonary dysplasia (moderate – severe) (Critical)
  • Neurodevelopmental Impairment

Physiological outcomes (which might apply to animal studies)

  • Measures of lung inflation
  • Pulmonary Blood flow
  • Blood gases

Study designs

The following study designs were considered for inclusion: animal studies, human trials (randomized, non-randomized, historically controlled) and human observational studies (cohort, before-and-after, case-control, case series if ≥6 participants). Literature was limited to articles in English, or in other languages providing there was an English abstract, with no date restriction.

Time Frame

From database inception to 30/12/2025

Search Strategies: Appendix 1 NLS 5325 Strategies for PPV

Inclusion and Exclusion criteria

Studies were eligible for inclusion if they directly or indirectly addressed the review questions.

Exclusion criteria: Studies were excluded if they had not been peer-reviewed and published in full text.

To 3080 records retrieved from searches, 15 records were added by citation searching of included articles. From the resulting 3095 records, 946 were removed as duplicates, resulting in 2149 titles and abstracts screened. Of these, 2089 were excluded and 60 full text articles were considered for inclusion. Of these, 19 were excluded as ineligible leaving 41 for inclusion in the review.

1. Why this topic was reviewed.

This topic was chosen for review by the NLS Task Force because PPV is considered a critical intervention during the resuscitation of a newborn who remains apnoeic, not breathing adequately, or bradycardic despite initial steps to promote breathing immediately after birth, and yet there are ongoing controversies as to the best strategies to provide it. The topic has not previously been comprehensively reviewed, using contemporary literature search and evidence appraisal strategies.

2. Narrative summary of evidence identified

For a summary of the included articles, see appendix. The 41 studies included examined:

  • Term infants: 11 {Bjorland 2022 222, Boon 1979 1031, Boon 1979 492, Ersdal 2020 78, Gomo Ø 2020 348, Holte 2021 128, Holte 2019 e000544, Hull 1969 58, Linde 2018 1, Linde 2017 80, Schmölzer 2015 844, Vyas 1986 189}
  • Preterm infants: 19 {Bhat 2017 910, Cavigioli 2023 555, Harris 2016 7, Hird 1991 69, Hunt 2019 670, Kaufman 2013 F410, Kibsgaard 2023 705, Mian 2019 F57, Murthy 2012 843, Murthy 2012 F249, Ngan 2017 F525, Rub 2025 1082, Schilleman 2011 920, Schilleman 2013 457, Schmölzer 2012 377, Shah 2023 e001768, Vaidya 2021 1930, van Vonderen 2015 F514, Yang 2020 605}
  • Preterm and term: 2 {Upton 1991 39, Vyas 1981 635}

Animal studies: 9* {Espinoza 2019 F98, Hillman 2007 575, Hooper 2013 e70895, Kuypers 2025 728, Pereira-Fantini 2023 L594, Probyn 2005 1764, Pryor 2020 891, Tingay 2023 589, Tingay 2015 890} *One study included both preterm animals and preterm infants 

Of these:, 21 examined PIP, 12 examined inspiratory time, 12 examined ventilation rate, 4 examined duration of PPV before reassessment, 9 examined exhaled tidal volume, 3 each examined synchronisation with spontaneous breaths and how to make adjustments and 2 examined methods to improve PPV. Thus, the studies examined one or more PPV variables, but none of them examined all of them or compared a bundle of variables (such as those included in contempoary guidelines with any other bundle. 

5325a - Peak Inflation pressure

There were no prospective studies that compared the use of different PIPs. Most observational studies used tidal volume (VT) as the outcome, while others examined heart rate recovery or ETCO2 measurements. Of the 21 studies that investigated peak pressures, 7 studies included a population of term neonates {Bjorland 2022 222, Boon 1979 1031, Boon 1979 492, Ersdal 2020 78, Holte 2019 e000544, Hull 1969 58, Vyas 1986 189}, 12 included preterm infants {Bhat 2017 910, Cavigioli 2023 555, Harris 2016 7, Hird 1991 69, Hunt 2019 670, Murthy 2012 843, Murthy 2012 F249, Schilleman 2011 920, Schilleman 2013 457, Schmölzer 2010 F393, Vaidya 2021 1930, van Vonderen 2015 F514} one included preterm and term neonates {Upton 1991 39} and there was one animal study. {Tingay 2023 589}

Vyas et al {Vyas 1986 189} investigated pressures generated during inspiration in 16 term infants and determined average peak pressures of 52 (range 28 – 105) cm H2O which led to VTe of 38 (6.5 – 69) mL and generation of a functional residual capacity (FRC) of 15 (0-32) mL. However, these were spontaneous inspirations generated by the infant rather than applied positive pressure and thus of limited value in informing any PPV strategy.

Observational studies in asphyxiated term infants requiring PPV reported an average PIP of 30 cmH2O to achieve lung aeration and establish FRC. These included studies of 20 intubated infants {Boon 1979 1031, Boon 1979 492} and 42 intubated infants ≥36 weeks. {Hull 1969 58} A study of 30 intubated infants between 36 and 42 weeks gestational age (GA) found that an initial PIP of 40 cmH2O led to adequate expiratory VT ; once an FRC was established, similar VT could be achieved with lower PIPs. {Upton 1991 39} Similarly, the provision of PPV with a SIB and face mask (with no PEEP) in two studies of 821 term infants and 434 mainly term, apnoeic infants, required an initial PIP of 30-40 cmH2O to establish an FRC. {Holte 2019 e000544} In a further study of 129 term newborns using a T-piece device with a PIP of 30 cmH2O and PEEP of 5 cmH2O, VT at the lower end of 4-8 mL/kg was delivered. {Bjorland 2022 222}

In a study of 70 newborn infants (59 intubated) between 24 and 35 weeks GA using observed chest wall movement as the marker of effective inflation, the median PIP was 22.8 cmH2O (range 14-30 cmH2O) but was higher (median 25 cm H2O) in those who did not establish regular respiration in the delivery room. {Hird 1991 69} VT was not measured. In preterm infants, a PIP of 20-25 cmH2O led to a VT below or at the lower end of 4-8 mL/kg when using a T-piece resuscitator with face mask., in studies including 64 infants 23-34 weeks, {Bhat 2017 910} 47 infants <32 weeks, {Cavigioli 2023 555} 11 infants 24-29 weeks, {Hunt 2019 670} 40 infants 26-32 weeks, {Murthy 2012 843} 30 infants 23-34 weeks, {Murthy 2012 843} 27 infants 27-31 weeks, {Schilleman 2013 457} and 15 infants <32 weeks. {van Vonderen F514} Schmölzer et al {Schmölzer 2010 F393} measured VTe in 20 preterm infants <32 weeks using either a T-piece resuscitator or SIB and found that a PIP (Mean ± Standard Deviation (SD)) of 26.3 (±8.8) cm H2O generated VTe median of 8.7 (IQR 5.3-11.3). Vaidya et al {Vaidya 2021 1930} measured PIP and VT in 10 very preterm infants (mean GA 23.9 weeks) who were intubated at birth and ventilated with T-piece resuscitator. The study described PIPs of 24.4 +/- 5 cm H2O and reported a large variation in delivered VT (median 5.7 (IQR 3.8-8.9) mL/kg), with 42% in the and author-defined target range of 4-6 mL/kg. In a study of 47 infants <34 weeks, Harris et al {Harris 2016 7} reported that using a T-piece device, mean PIPs of 25 cm H2O, provoked active inspiratory efforts, which they concluded was via Head’s paradoxical reflex, whereas those of 21 cm H2O did not.

The available data suggest that at birth intial PIPs of 30-40 cmH2O for term, and 25-30 cmH2O for preterm may be reasonable for the inadequately aerated liquid filled lung. Lower PIP’s may fail to clear airway liquid leading to suboptimal VT and inhomogenous ventilation. Lower PIPs may be sufficient once the lung is aerated and compliance improves. However, these conclusions will require verification in a systematic review in which the risk of bias for each study and overall certainty of evidence is appraised.

When using a T-piece device, gas flow rates are a potential confounding factor as changes in flow rates without compensatory changes of the resistance through the PEEP valve causes significant changes in PEEP, PIP and delivered VT {Schilleman 2011 920} as well as expiratory resistance. With a T-piece, flow rates are set and rarely change during resuscitation. Whilst flow rates were different between studies, they did not vary within each study. However, when using an SIB, inspiratory flow is influenced by the effort of the operator and without a manometer, peak pressures are not controlled, unknown and may vary considerably between inflations.

Care needs to be taken when interpreting results, as end expiratory pressures used in various studies varied, as is inevitable given that some studies used SIBs, most of which cannot deliver reliable PEEP, whereas others used T-piece devices which usually have PEEP valves. Hence the inflation pressures (the difference between PIP and PEEP) in studies vary. The effect of PEEP on helping alveolar recruitment (and increasing lung compliance) may significantly affect the magnitude of inflating pressure (and PIP) required once the lung is aerated, which may also influence lung injury {Tingay 2023 589}. Since there is biological and device variation and the Vte is determined not just by peak or inflating pressure but also by other variables such as inspiratory time, and FRC by the presence/absence of PEEP it is entirely plausible that the optimal PIP depends on individual patient circumstances, including the setting and the devices available.

5325b and 5325c- Inflation time and Rate of PPV

No prospective studies in human infants compared different inflation times (Ti) <5 seconds on VT recruitment at birth. A total of 9 studies were identified where inflation time and rate of PPV were investigated: 4 studies included a population of term neonates {Bjorland 2022 222, Boon 1979 1031, Gomo Ø 2020 348, Holte 2019 e000544} 3 included preterm infants {Bhat 2017 910, Harris 2016 7, Vyas 1981 635} and there were two animal studies. {Kuypers 2025 728, Pryor 2020 891}

An experimental randomised animal study in 28 preterm rabbits compared Ti’s of 0.2 and 1.0 sec on VT and FRC and reported that PPV with a longer Ti increased the rate of Vt and FRC recruitment (measured using phase contrast X-ray imaging). {Pryor 2020 891} The authors argued that short inflation times of (such as the 0.3–0.5 sec recommended by contempory guidelines) may not be the most effective way of supporting very preterm infants immediately after birth when the lung is partially liquid-filled and that longer Ti’s increase the uniformity of lung aeration and efficiency of gas exchange. In a retrospective analysis of 64 preterm neonates of <34 weeks gestational age requiring resuscitation at birth, infants were divided into 4 groups depending on the inflation pressure (IP = PIP-PEEP) (<20 or >20 cmH2O) and Ti (<1.5 or >1.5 sec) received during the first 5 inflations. {Bhat 2017 910} While an increased Ti was significantly associated with an increased VT, this relationship was lost for IP >20 cmH2O and when infants that didn’t develop a VT in the first 5 inflations were excluded. In a study of 9 intubated infants (31-43 weeks), Vyas {Vyas 1981 635} determined that a single inflation after birth with a Ti of 5 sec followed by PPV with a Ti of 1 sec produced a significantly higher VT (33.6ml) than an initial inflation time of 1 sec used in a previous study (18.6ml). {Boon 1979 1031} (33.6 vs 18.6 mls). These authors postulated that the single longer breath enabled greater recruitment of the liquid filled lung. In a study of 47 infants <34 weeks gestation, Harris reported that a longer Ti (mean >1.6 sec) compared to a shorter Ti (mean 0.8 sec) provoked active inspiratory efforts most likely through prompting respiratory reflexes. {Harris 2016 7}

Three large observational studies examined ventilation parameters including rate and inflation time during mask PPV. Holte {Holte 2019 e000544} examined 434 newborns, mostly >37 weeks, ventilated with a self-inflating bag (no PEEP) and used expired CO2 (ECO2) as an indicator of lung aeration as previously demonstrated in animals and humans {Hooper 2013 e70895, Ngan 2017 F525, Schmölzer 2015 844}. The developing VT was closely associated with increasing ECO2 levels. Increasing ventilation rate (VR) above 30 inflations/min was closely associated with decreasing ECO2 levels. {Holte 2019 e000544} Gomo using similar methodology in a study of 198 newborns mostly >37 weeks ventilated with a self-inflating bag with a PEEP valve reported that higher VRs (>60 inflations/min) were associated with lower expired VT levels. {Gomo Ø 2020 348} Bjorland included 129 term newborns ventilated with a T-piece (PIP of 30 cmH2O and PEEP of 5 cmH2O and measured the VT delivered by 6,541 inflations, dividing the inflations into early phase (first 20) and late phase (>20) inflations. During the early phase, VT rapidly increased with increasing Ti until a Ti of 0.41 sec after which there was a more gradual increase until a Ti of approximately 1.2 sec, with no further increase in VT after. In the late phase, a Ti of approximately 0.5 sec was associated with increased VT. Ventilation rates of 30-40/min were associated with increased VT during both phases. {Bjorland 2022 222}

Taken together, the included studies suggest that, for a given PIP, the VT continues to increase with increasing Ti up to 1.2 sec during lung aeration. Once the lung is aerated, an inflation time >0.5 secs and inflation rates of 30-40/min appear to deliver the highest VT, with greater FRC accumulation and increasing lung compliance. There is no evidence to suggest that longer Ti increases the risk of lung over-inflation. Again, these conclusions need to be confirmed in a systematic review that assesses risk of bias and overall certainty of evidence.

The inspiratory time of initial inflations and their effect on lung recruitment and VT are still not well defined, nor is the optimal target VT (see below) although a low VT, which is approximately equal to the physiological dead space (~3mL/kg), may not be optimal. Studies suggest that, at birth, initial inflation times longer than those used during conventional PPV within the Neonatal Intensive Care Unit (NICU) are more effective at achieving an adequate VT as a result of the difference in mechanics of the liquid-filled (vs air-filled) lung at this time.

These studies did not examine the influence of the expiratory interval on VT and FRC recruitment. Expiratory braking may be significant. In an animal model using preterm rabbits, increased expiratory resistance reduced deflation rates and helped maintain FRC levels {Kuypers 2025 728}.

5325d – Duration of PPV before assessing need to change strategy

For the duration of PPV before assessment, 4 studies were included: 2 included term infants {Holte 2019 e000544, Linde 2017 80} 1 included preterm infants {Kibsgaard 2023 705} and there was one relevant 1 animal study. {Espinoza 2019 F98}

Kibsgaard showed that the HR did not increase until at least 20 sec of PPV in 98 bradycardiac newborn infants ≥30weeks GA receiving PPV via a SIB or T-piece resuscitator at recommended settings (30/5 cmH2O starting at room air for neonates of ≥32 weeks GA, and 25/5 cmH2O at FiO2 0.30 for newborns of <32 weeks GA). {Kibsgaard 2023 705}. In a study of 30 hypoxic bradycardic intubated term 1 day old newborn piglets, who had already transitioned to newborn life, a HR response was only observed after 30 sec of PPV, with no HR response in the first 20 sec {Espinoza 2019 F98}. Linde reported the HR response of 215 term newborns when PPV with a SIB was delivered in 20 sec sequences with pauses for HR assessment. Most newborns had progressive HR increases with or without PPV (suggesting they may have been in primary apnoea), and the most significant HR increase occurred when the HR was initially less than 100 bpm. {Linde 2017 80} Pauses between periods of PPV delivered by SIB without PEEP result in derecruitment and a need to re-establish the FRC. {Holte 2019 e000544}

Taken together, the studies suggest that PPV should be delivered for at least 20 seconds before reassessing HR response. Pauses in PPV should be minimised.

5325e – Exhaled Tidal Volume

Vte is a pragmatic marker of the effectiveness of PPV and can be measured during interventions. A total of 10 studies were identified where exhaled tidal volume was measured: 3 studies assessed term infants, {Holte 2021 128, Holte 2019 e000544, Linde 2017 80} 2 assessed preterm infants, {Mian 2019 F57, Rub 2025 1082} one both preterm infants and animals {Hooper 2013 e70895} and there were 4 animal studies. {Hillman 2007 575, Pereira-Fantini 2023 L594, Probyn 2005 1764, Tingay 2015 890}

In a study of 132 preterm infants ventilated with a T-piece with PEEP, a minimum VTe of 4mL/kg was required to provoke an increase in the heart rate. {Rub 2025 1082} In a study of 215 mostly term asphyxiated apnoeic newborns resuscitated with face-mask and SIB (no PEEP), VT ≥6 mL/kg was needed to increase HR, with the fastest HR rise observed at ~9 mL/kg. {Linde 2017 80} In a study investigating the relationship between ECO2 and VT in intubated newborn lambs and rabbit pups and mask-ventilated preterm infants, exhaled CO2 (ECO2) correlated to VT and to lung volumes measured by phase contrast in rabbits. {Hooper 2013 e70895} In the preterm infants ECO2 level increased to >10mmHg [(median 28(IQR 21-26)] before the HR increased to >100 bpm. {Hooper 2013 e70895} In a study of 434 apneic mostly term newborns, ETCO2 increased non-linearly with VT up to >10 mL/kg, while VT of 10-14 mL/kg achieved fastest ETCO2 response. {Holte 2021 128, Holte 2019 e000544} Each minute delay in achieving ETCO2 >2% and HR >100 bpm/min was associated with a decreased 24-h survival of 17% and 44%, respectively. In a study of 165 preterm infants <29 weeks, VT of greater than 6 mL/kg was associated with significantly increased rates of severe intraventricular hemorrhage (20% vs 6% p=0.01). {Mian 2019 F57} In a study of 38 very preterm lambs, higher initial VT and abrupt VT reduction during PPV increased ventilation heterogeneity and lung injury. {Pereira-Fantini 2023 L594} In a study of 28 preterm lambs ventilated from birth with supraphysiological VT (15 mL/kg) for 15 minutes, inflammatory lung injury was evident and increased with continuing PPV. {Hillman 2007 575} In a study of 24 preterm lambs incremental increases in delivered VT from 3mL/kg to 7mL/kg led to increased heterogenity of aeration and impaired oxygenation in gravity dependent lung compared to a constant 7mL/kg. {Tingay 2015 890} In another animal study involving 20 very premature lambs at 125 days gestation resuscitated for 15 minutes, the group ventilated with a tidal volume of 5ml/kg and a PEEP of 8 cmH2O had mean (SD) PaCO2 levels of 64.1 (±5.6) mmHg indicating underventilation, whereas those ventilated with a tidal volume of 10mL/kg and a PEEP of 8 cmH2O had mean PaCO2 of 27.9 (±2.3) mmHg, indicating overventilation. {Probyn 2005 1764}

The included studies suggest that higher expired VTe may improve heart rate and ventilation effectiveness in term asphyxiated infants but could be associated with increased lung injury and severe intraventricular hemorrhage in preterm infants. Optimal VTe may differ with maturity—higher VT benefiting term infants during resuscitation, whereas lower, carefully controlled volumes, avoiding significant changes are important, to minimize injury and improve aeration, particularly in extreme preterm infants.

5325f – Synchrony of inflations with spontaneous breathing

Studies of inflations synchronised with spontaneous breaths during mask PPV in the delivery room are limited to observational studies evaluating respiratory function monitor (RFM) recordings. Therefore, it is not possible to distinguish between intentionally timed synchrony by the resuscitator with the infant’s spontaneous breath or by chance co-incidental, synchronised inflations during PPV. Four studies, all in preterm infants, investigated synchrony and were included. {Kaufman 2013 F410, Murthy 2012 F249, Schilleman 2013 457, van Vonderen 2015 F514}

Kaufman et al performed a secondary analysis of an RCT evaluating utility of respiratory function monitoring in the delivery room (masked vs visible screen during neonatal stabilisation). {Kaufman 2013 F410} In this observational cohort study, 2,605 inflations and breaths were analysed from 29 preterm (<32 week gestation) infants using repeated measures ANOVA. Ventilation was documented either as an inflation not associated with a spontaneous breath (asynchronous) or assisted inflations (synchronous with a spontaneous breath). Analysis of 1,821 inflations, after excluding 64 spontaneous breaths between PPV and 720 breaths during CPAP, found no significant difference in VT. 283 (16%) were assisted (synchronised), resulting in a median VT of 9.3 (IQR 4.5-11.8) mL/kg, whereas the remaining 1538 inflations not associated with a spontaneous breath resulted in a VT of 8.3 (IQR 5.7-10.7) mL/kg (p=1.0).

Three studies reported that spontaneous breaths coinciding with inflations did increase VT. Schilleman et al reported 1,643 inflations from 27 infants less than 32 weeks’ gestation and reported larger VT for breaths that coincided with inflations (median 4.5mL/kg) compared to all inflations (median 3.6mL/kg, p<0.01). {Schilleman 2013 457} Murthy et al reported similar findings in a study of 30 preterm infants <34 weeks receiving mask PPV with lower Vte with passive inflations (median 2.1mL/kg (range 0-19.8 mL/kg)) compared to active inflations median (5.6 mL/kg (range 1.2 -12.2 mL/kg)). {Murthy 2012 F249} Van Vonderan et al studied 15 infants <32 weeks’ GA stabilised at two tertiary neonatal centres. They measured a total of 487 PPV inflations of which 188 coincided with breaths (39%). {van Vonderen 2015 F514} The study concluded that VTi, VTe and ECO2 were significantly larger during inflations that coincided with spontaneous breaths when compared to inflations only.

Taken together, these studies suggest that synchrony could be important in optimising gas exchange, which is mediated by higher VT. They suggest that newborn infants’ spontaneous breaths may contribute to achieving a higher VT for any given PIP. However, there is insufficient evidence to determine whether there is merit to an overall strategy of trying to synchronize PPV with spontaneous breaths during resuscitation. Mechanical ventilation, allowing the potential for sensitive triggering of inflations using pneumotachography, could offer better synchonization compared to manual PPV, but has not been addressed in any included study.

5325g – Optimisation of PPV/ Adjustment after initial PPV

Two studies investigated optimisation of PPV through adjustments in preterm infants. {Shah 2023 e001768, Yang 2020 605} In a study of 25 preterm infants <30 weeks gestation, a two-person approach to face mask application with jaw support reduced percentage mask leak compared to a single-handed method (mean(SD) 26.4 (±18.5) vs 17.6 (±9.3) p=0.018) but did not increase mean VT. {Shah 2023 e001768} In preterm infants <32 weeks, 12 of 41 observed ventilation corrective steps increasedVT, 6 decreased it, and 20 produced no change, highlighting variable effects on ventilation. {Yang 2020 605}

Use of RFM shows potential for optimizing PPV in the delivery room e.g. Schmölzer et al {Schmölzer 377} However an ILCOR systematic review of RFM in clinical settings (and more recent evidence update) found no improvement in clinical outcomes when RFM was used. {Fuerch 2022 100327, Liley 2025 }

Two recently published guidelines set out different consensus-based sequences of airway and breathing optimization steps. {Hogeveen 2025 110766, Lee 2025 S385} Whilst a context relevant rather than didactic approach to airway/breathing strategy might be considered logical to secure airway patency and optimize lung inflation, it must be informed by assessment of HR after sufficient time to expect a response. However, there are no comparative studies to determine the superiority or inferiority of any given approach.

5325h – Guideline recommendations

There are no studies directly comparing the outcomes of resuscitation at birth under different international guideline approaches in either humans or animal models. While some animal studies have varied their ventilation strategies, these do not align precisely with the protocols of specific resuscitation guidelines. Human studies, in turn, typically follow the algorithm used within the investigators’ institution. Comparisons of the major guidelines, such as those from the AHA/ Neonatal Resuscitation Program (NRP) and ERC/ Newborn Life Support (NLS) have focused on procedural differences rather than outcomes. {Ramaswamy 2021 151} The WHO/EENC {World Health Organisation 2022 } offer additional recommendations adapted for resource-limited settings. Despite all being based on the best available evidence and ILCOR CoSTR reviews, the persistence of notable differences reflects the absence of definitive physiological or outcome-based evidence to guide practice.

Recommendations rely on expert consensus and tradition, both for the most part based on individual studies rather than rigorous systematic reviews. One striking divergence lies between ERC/NLS and AHA/NRP approaches to initial inflations. The ERC advocates five prolonged inflations (2–3 s) at higher pressures (30 cmH2O for term, 25 cmH2O for preterm) before transitioning to ventilation at a rate of 30 breaths/min {Hogeveen 2025 110766, Madar 2021 326}, whereas the NRP promotes immediate PPV at 30-60 breaths /min with lower pressures (20-30 cmH2O) and shorter inspiratory times. {Aziz 2021 e2020038505E, Lee 2025 S385} Lower starting pressures are typically suggested for preterm infants but there is a lack of evidence-based adaptation for the delivery of PPV to preterm infants at birth. At this stage. there are no prospective human infant trials to establish the superiority or inferiority of either approach.

In a study of near-term asphyxiated lambs, a SI achieved faster recovery of HR and cerebral blood pressure than either a series of short sustained inflations (equivalent to NLS) or immediate PPV with shorter inflation times (equivalent to NRP), suggesting potential advantages of prolonged initial inflations. {Klingenberg 2013 F222} An ILCOR systematic review found no benefit and possible harm for inflations longer than 5 seconds in preterm human infants. {Kapadia 2021 e2020021204} Hence ILCOR has suggested against sustained inflations longer than 5 seconds in preterm infants, but due to insufficient evidence, made no recommendation for late preterm or term infants. {Liley 2025 , Wyckoff 2020 S185}

No studies have yet evaluated the combined elements of PPV variables and guideline recommendations to determine their overall effects on lung recruitment, gas exchange, or neonatal outcomes in either term or preterm infants. Regardless of the guideline followed, clinicians must tailor their interventions to the infant’s physiological response, adjusting positive pressure ventilation in real time according to changes in heart rate, lung compliance, and spontaneous respiratory effort.

3. Task Force Insights / Narrative Reporting of the Task Force Discussions

The topic of strategies for PPV for newborn infants needing resuscitation was reviewed because PPV is considered a key intervention, and the last guidance on specific strategies was developed in 2010. {Perlman 2010 S516} The review identified studies since 2010 that address aspects of PPV strategy including PIP, TI use of tidal volume monitoring to guide PPV, and the infant’s responses to PPV that may enable judgements about how long to use a particular strategy before making adjustments. Most human infant studies were observational and addressed only short term physiological outcome measures. There are many gaps in the published literature. There were no RCTs or even pilot interventional studies on which future large RCTs could be based, or large observational comparative studies that met our inclusion criteria and directly addressed the PICO questions posed for the review. Most included studies focus on a single PPV component, whereas relevant animal studies demonstrate confounding interactions between PPV variables that prompt caution when evaluating any PPV component in isolation. There is a lack of trials comparing different bundled approaches/strategies and a lack of data on longer term outcomes. Nevertheless, the Task Force concluded that a systematic review is required to update the 2010 treatment recommendation, although despite new studies, the certainty of evidence, assessed using contemporary methods, is likely to be low or very low. It is apparent from the scoping review that RCTs or other types of intervention studies (e.g. cluster randomized or crossover trials) of different PPV strategies are needed, taking into account the initial and subsequent physiological phases of PPV and variations in gestation and underlying reasons for the need for PPV.

Treatment Recommendations

The treatment recommentation from 2010 states ”There is no evidence to support the use of inflation pressures higher than those that are necessary to achieve improvement in heart rate or chest expansion. This can usually be achieved in term infants with an inflation pressure of 30 cm H2O (LOE 4) and in preterm infants with pressures of 20 to 25 cm H2O (LOE 4). Occasionally higher pressures are required (LOE 4). In immature animals, ventilation at birth with high tidal volumes associated with the generation of high peak inflation pressures for a few minutes causes lung injury, impaired gas exchange, and reduced lung compliance (LOE 5)” {Perlman 2010 S516}

The term LOE 4 referred to studies considered at high risk of bias including case series, cohort studies or case-control studies, and LOE 5 to indirect evidence and expert opinion.

The results of this scoping review suggest that this recommendation can be updated with more recent evidence and a systematic review is justified, using contemporary evidence appraisal methods.

The uncertain reliability of observations of chest expansion, {Aufricht 1993 139, Stenson 1995 257} the delayed improvement in heart rate after commencing or improving PPV {Espinoza 2019 F98, Kibsgaard 2023 705} and the poor prediction of VTe from PIP raise concerns that better methods are needed to enable adjustment of any PPV strategy at birth to meet individual infants’ needs.

Knowledge Gaps

  • RCTs or large comparative trials addressing optimum starting pressures, inspiratory and expiratory times, rate, duration, Vt or subsequent optimizing strategies in term, preterm and in particular extremely preterms infants at birth.
  • RCTs that consider the interaction between PPV variables in their design (eg between PIP and Ti) and how these variables change with lung aeration.
  • Such studies should consider the effects of biological variation between infants and the devices and interventions used.
  • Studies should consider the metrics (and defined ideal values) by which delivery of PPV are measured
  • Studies should consider both high and lower resource settings.

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Appendix 1 NLS 5325 Strategies for PPV

Appendix 2 NLS 5325 Strategies for PPV

Appendix 3 NLS 5325 Strategies for PPV

Glossary


Neonatal, Neonatal Life Support, NLS, NLS 5325, 5325, ventilation

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