Oxygen Therapy in Neonates NNFI CPG Dec2021

Clinical Practice
Guidelines

Oxygen Therapy in

Neonates

December 2021

National Neonatology Forum, India
Oxygen Therapy in Neonates
Guideline Writing Group (Alphabetical)
Gopal Agrawal
Shamsher Singh Dalal
Ajoy Kumar Garg
Rajesh Kumar
Sachin Shah
Daljit Singh (Chairperson)
Reviewers (Alphabetical)
Deepak Chawla
Aakash Pandita
Anu Sachdeva
Editorial Board (Alphabetical)

Aparna Chandrasekaran
Deepak Chawla
Praveen Kumar (Chairperson)
M Jeeva Sankar
Sachin Shah
Sindhu Sivanandan
Vishal Vishnu Tewari
Disclaimer
Due care has been taken to verify the accuracy of the information in this Clinical
Practice Guideline. However, the contributors, editors or National Neonatology Forum
are not responsible for any errors or omissions, or for any consequences from the
application of information provided here and give no guarantee with respect to the
completeness or accuracy of the contents. Application of the information in a
situation different from that described in guidelines remains the professional
responsibility of the concerned physicians. The guidelines do not endorse any
particular brand of equipment or drug.
The contributors and editors have made effort to ensure that all information is
according to currently accepted recommendations. However, given the rapidity with
which new information emerges, the reader is urged to check for latest updates.
© NNF India Online Version www.nnfi.org/cpg December 2021

Oxygen Therapy in Neonates 9
EXECUTIVE SUMMARY
Oxygen is the most used drug in healthcare of sick neonates. While oxygen administration
corrects hypoxia in various neonatal conditions, like any other drug, oxygen may also cause
significant side effects. Repeated or prolonged hyperoxia leads to oxidative stress and cell
injury. In view of evidence suggesting adverse outcomes of hyperoxia in both term and
preterm neonates, evidence-based recommendations should guide the oxygen therapy.
Apart from titration of oxygen therapy, this guideline document also addresses the need of
humidification and various technological choices in monitoring and titrating oxygen therapy.
This guideline applies to neonates who require oxygen or respiratory support in the first few
weeks after birth. This guideline is not meant to address the practice issues about the use of
oxygen during neonatal resuscitation. The guideline is meant to be used by all levels of
healthcare workers, from neonatologists to nurse practitioners involved in the care of
neonates, and in all the healthcare settings including newborn stabilization units (NBSU),
special newborn care units (SNCU) neonatal intensive care units (NICU).
The guideline has been developed following the process described in the Grading of
Recommendations Assessment, Development, and Evaluation (GRADE) Handbook and WHO
Handbook for guideline development. The Guideline Development Group (GDG) identified 8
research questions about the use of oxygen in neonates to be of highest priority. Three of these
questions detailed the oxygen saturation targets in different gestational age/ disease groups,
while two questions dealt with the modes of oxygen delivery. Two questions evaluated the
techniques to monitor oxygenation status including continuous versus intermittent pulse
oximetry as well as the type of pulse oximeter. The last question evaluated the role of closed
loop FiO2 control to improve the time spent within oxygen saturation targets. The GRADE
approach was used for grading the certainty of evidence after adaptation to the relevant
working area. The certainty of evidence for an outcome was graded as high, moderate, low
or very-low. After grading the available studies for each outcome, recommendations were
based on the certainty of evidence, balance between benefits and harms, values and
preferences of policymakers, health-care providers and parents, feasibility and resource use
and whether costs are justifiable relative to benefits in the Indian setting.
Each recommendation was graded as strong when there was confidence that the benefits
clearly outweigh the harms, or weak when the benefits probably outweigh the harms, but
there was uncertainty about the trade-offs. If the GDG judged that the benefits of a
recommendation outweigh the harms only in certain specific situations but not in others, the
recommendation was labelled as situational /context specific.
A summary of the key recommendations is listed next in the table.
NNF India Evidence-based Clinical Practice Guidelines December 2021

SUMMARY OF RECOMMENDATIONS FOR OXYGEN THERAPY IN NEONATES
S. No. Recommendations Strength of Certainty of evidence

Recommendations
1. All preterm neonates born at ≤34 weeks Strong High for less than 28
of gestational age and requiring weeks’ gestational
respiratory support should be managed age
using oxygen saturation target of 91-95%
in preference to lower(85-89%) oxygen Moderate for 28-34
saturation targets. weeks’ gestational
age
2. All neonates born at >34 weeks of Weak Not graded

gestational age
and requiring respiratory support may
be managed using oxygen saturation
targets of 91-95% in preference to lower
(85-89%) oxygen saturation targets.
3. All neonates with evolving / established Strong High

BPD and requiring respiratory support
should be managed using oxygen
saturation targets of 91-95% in
preference to higher (95-98%) oxygen
saturation targets.
4. In neonates born at >34 weeks of Strong Moderate

gestation and with mild respiratory
distress, nasal cannula with low flow rate
(0.5 - 1 L/min) should be used for
delivering oxygen in preference to
oxygen by hood or incubator oxygen.
5. In neonates being administered oxygen Weak Not graded

at high flow rate (>1 L/min) through
nasal cannula, warming and
humidification of the inhaled gases may
be preferred over no warming and
humidification.
Warming and humidification may not
be necessary when flow rate through
nasal cannula is low (< 1 L/min).

6. In neonates on any respiratory support, Strong Not graded

oxygen saturation may be monitored
continuously in preference to
intermittent monitoring.
7. In neonates on respiratory support pulse Strong High

oximeters with or without signal
extraction technology may be used for
monitoring of oxygen saturation.
8. The guideline panel does not Weak Very low

recommend for or against the use of
closed-loop oxygen therapy in neonates
on respiratory support.

INTRODUCTION
Administration of oxygen to neonates improves survival in situations where lung immaturity,

infection or other pulmonary conditions reduce the arterial oxygen concentration. Goals of
oxygen therapy in these neonates are to: (i) supply sufficient oxygen to the tissues, thus
avoiding anaerobic metabolism and lactic acidosis; (ii) prevent hypoxic pulmonary
vasoconstriction, which may worsen hypoxemia in a vicious circle resulting in hypoxic injury to
critical organs; and (iii) promote brain and somatic growth. Oxygen, like any other drug, has
potentially dangerous side effects. The ideal oxygen therapy should meet these goals while
minimizing formation of oxygen free radicals. Oxygen therapy in neonates is a balance of
competing adverse outcomes. In extreme premature neonates there is an increased risk of
death and neurodevelopmental disability at the lower saturation ranges but an increased risk
of retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD) at the higher
saturation range. Similarly, in more mature neonates (late preterm and term neonates) there
is risk not only of worsening pulmonary vascular resistance and hypoxic brain injury with lower
oxygen saturations but also of oxidative stress causing free radical injury to multiple organs,
including lungs and brain, and poor outcome with higher oxygen saturation.
Improvements in technology in the past few decades have led to the increased survival of
preterm and low birth weight infants. One of these advances is the ability to measure oxygen
levels more accurately. Pulse oximetry has gradually become the most widely used method of
monitoring oxygenation because of its non-invasive nature, ease of application and lower cost
as compared to arterial blood gas analysis and continuous transcutaneous PO2 monitoring.
SCOPE OF THE GUIDELINES AND TARGET AUDIENCE
Scope
This guideline applies to neonates who require oxygen or respiratory support in the first few
weeks after birth. This guideline does not address oxygen use in delivery room or during
neonatal resuscitation.
Target audience
The primary audience for this guideline includes health-care professionals (pediatricians and
nurses) responsible for delivering care to neonates in different levels of heath care, health
program managers and policymakers in all settings. The information in this guideline will be
useful for training of health professionals and developing job aids. Health policymakers may
also use these guidelines to plan or upgrade facilities in special newborn care units (SNCUs) for
optimal care of infants.
Population of interest
The guidelines focus on the use of oxygen in term and preterm neonates admitted to
healthcare settings with various respiratory conditions in India. This guideline is not meant for
oxygen use in delivery room or during neonatal resuscitation.

METHODOLOGY
The GDG identified 8 high priority clinical practice questions on the use of oxygen in neonates
(Panel 1). Each of these questions deserved separate systematic reviews, taking into
consideration the critical and important outcomes. GDG members and external experts peer-
reviewed the systematic review. Panel 2 lists the critical and important outcomes considered
relevant for this review.
Panel 1 : Prioritized Clinical Practice Questions
Questions on oxygen saturation targeting

1. Among preterm neonates born at ≤34 weeks’ gestational age and on any respiratory
support, do “higher oxygen saturation targets (91-95%)” compared to “lower oxygen
saturation targets (85-89%)” affect mortality or severe morbidities?
2. Among preterm neonates born at >34 weeks’ gestational age and on any respiratory
support, do “higher oxygen saturation targets (91-95%)” compared to “lower oxygen
saturation targets (85-89%)” affect mortality or severe morbidities?
3. Among preterm neonates (born at <37 weeks gestational age) with established/ evolving
chronic lung disease/bronchopulmonary dysplasia, do “standard saturation targets (91-95%)”
compared to “higher saturation targets (96-98%)” affect the incidence of mortality or severe
morbidities?
Modes of oxygen delivery

4. Among neonates born at ≥34 weeks gestational age with mild respiratory distress, does
“oxygen by hood or oxygen by incubator” compared to “oxygen by nasal cannula” affect
mortality or severe morbidities?
5. Among neonates on oxygen support by nasal cannula (low/high flow), does
“humidification” compared to “no humidification” affect mortality or severe morbidities?
Monitoring oxygenation
6. Among neonates on any respiratory support, does “intermittent monitoring of oxygen
saturation” compared to “continuous monitoring of oxygen saturation” affect mortality or
severe morbidities?
7. Among neonates on any respiratory support, does use of “pulse oximeter with signal
extraction technology (SET)” compared to “non-SET pulse oximeter” affect mortality or severe
morbidities?
Techniques to improve compliance to oxygen saturation targeting

8. Among neonates on any respiratory support, does use of “automated closed loop
regulation” compared to “manual regulation” of fractional oxygen delivery to achieve desired
saturation targets affect mortality or severe morbidities?
OUTCOMES ASSESSED
Critical and important outcomes assessed in this guideline are summarized in Panel 2. Benefits
and harms in critical outcomes formed the basis of the recommendations. When information
on critical outcomes was not available, non-critical outcomes formed the basis of a
recommendation.

Panel 2: Outcomes considered for this review
Relevance Outcomes Definition

Critical Neonatal mortality All-cause death in the first 28 days of life
In-hospital mortality All-cause death during the initial hospital stay
Bronchopulmonary Use of supplemental oxygen at 36 weeks
dysplasia (BPD) postmenstrual age
Neurodevelopmental Moderate or severe neurodevelopmental
morbidity impairment (NDI) at or after 12 months of age
(including cerebral palsy, mental retardation,
developmental delay, blindness, deafness) rates
Retinopathy of ROP requiring laser/cryotherapy
prematurity (ROP)
Important Respiratory failure Respiratory failure, as defined by clinical
needing mechanical (worsening retractions, tachypnea/apnea with or
ventilation without cyanosis) and laboratory (hypoxia and/or
hypercapnia) criteria, which requires respiratory
support in the form of assisted ventilation
Patent ductus arteriosus PDA needing medical or surgical treatment
(PDA)
Necrotizing enterocolitis Stage 2 to 3 NEC, defined as per modified Bell’s
(NEC) criteria
Sepsis Clinical features of sepsis with or without isolation
of organisms from blood/CSF/urine and
laboratory parameters suggestive of sepsis
Duration of Duration of hospital stay from birth/initial
hospitalization admission till discharge or death
Duration of oxygen Duration of oxygen therapy in days

therapy
Time within target SpO2 Duration of time spent in target saturation range
range as percent of total monitored time
SELECTION OF STUDIES
Search strategy
Keywords: (infant, newborn) AND (Newborns, oxygen inhalation therapy, oxygen, oxygen
therapy).
We used the standard search strategy and searched Medline via PubMed, Embase and
Cochrane Central Register of Controlled Trials for systematic reviews and randomized
controlled trials (RCTs) published. Wherever RCTs were unavailable, observational studies were
used for framing the recommendations.
Using the assembled list of priority questions and critical outcomes from the scoping exercise,
the GDG identified systematic reviews that were either relevant or potentially relevant and

assessed whether they needed update. A systematic review was out-of-date if the last search
date was one year or more prior to the date of assessment. The GDG updated out-of-date
systematic reviews relevant to this guideline. Cochrane Systematic Reviews were the primary
source of evidence for the recommendations included in this guideline. In addition, key
databases searched included the Cochrane Database of Systematic Reviews of RCTs, the
Cochrane Controlled Trials Register and MEDLINE (1966 to 2019). The reference lists of relevant
articles were also searched to identify relevant studies.
Data abstraction and summary tables of individual studies
A standardized form was used to extract information from relevant studies. Systematically
extracted data included: study identifiers, setting, design, participants, sample size,
intervention or exposure, control or comparison group, outcome measures and results. The
following quality characteristics were extracted for the RCTs: allocation concealment, blinding
of intervention or observers, loss to follow up, and intention to treat analysis. The studies were
stratified according to the type of intervention or exposure, study design, birth weight and
gestational age, where possible. Treatment effect was expressed as relative risks (RR) or odds
ratios (OR) for categorical data, and as mean differences (MD) or weighted mean differences
(WMD) for continuous data.
Pooled effects
Pooled treatment effect for developing recommendations were considered, wherever

feasible. Pooled effects from published systematic reviews were used if the meta-analysis was
appropriately done, and the reviews were up to date. Where pooling of results was not
possible, the range of effect sizes observed in the individual studies was used in the
development of recommendations.
Grading the quality of evidence
Quality assessment of the body of evidence for each outcome was done using the Grading
of Recommendations Assessment, Development and Evaluation (GRADE) approach. The
GRADE approach was used for all the critical outcomes and a GRADE profile was prepared
for each quantitative outcome. Accordingly, the certainty of evidence for each outcome was
rated as “high”, “moderate”, “low”, or “very-low” based on a set of criteria. As a baseline, RCTs
provided “high-certainty” evidence, while non-randomized trials and observational studies
provided “low-certainty” evidence. This baseline quality rating was then downgraded based
on consideration of risk of bias, inconsistency, imprecision, indirectness, and publication bias.
The following briefly describes how these criteria were used:
Study design: We included only randomized controlled studies. Observational studies, and
non-randomized experimental studies were considered for narrative review. Four criteria were
used for assessing limitations in the methods of included studies; 1) Selection bias was assessed
by analyzing how randomization and allocation concealment was done 2) Measurement bias
can be minimized by blinding the participants and researchers to the intervention. If that is not
possible, the observers measuring outcome can be blinded. Measurement bias was less likely
if the outcome is "objective". If most of the evidence was from studies where any of the above
was done, the risk was low, otherwise it was considered high 3) Loss to follow-up: A large loss

to follow-up can lead to bias in results; 20% loss to follow-up was chosen arbitrarily as the cut-
off point. If most of the evidence was from studies where loss to follow-up was less than 20%,
the risk was low 4) Appropriateness of analysis: If most of the evidence was from RCTs which
had analysis by intention-to-treat the risk of bias was low, else it was high.
Inconsistency of the results: The similarity in the results for a given outcome was assessed by
exploring the magnitude of differences in the direction and size of effects observed from
different studies. The quality of evidence was not downgraded when the directions of the
findings were similar and confidence limits overlapped, whereas quality was downgraded
when the results were in different directions and confidence limits showed minimal overlap.
Indirectness: The quality of evidence was downgraded on serious or very serious concern
about the directness of the evidence, i.e., important differences between the research
reported and the context for which the recommendations are being prepared. Such
differences were related, for instance, to populations, interventions, comparisons, or
outcomes.
Imprecision: The degree of uncertainty around the estimate of effect was assessed. As this
was often a function of sample size and number of events, evidence from studies with
relatively few participants or events (and thus wide confidence intervals around effect
estimates) were downgraded for imprecision.
Publication bias: Quality rating could also be affected by perceived or statistical evidence of
bias that may have led to underestimation or overestimation of the effect of an intervention
because of selective publication based on study results. Where publication bias was strongly
suspected, evidence was downgraded by one level.
Formulation of recommendations
After grading the available studies for each outcome, recommendations were formulated
based on the summary and quality of evidence, balance between benefits and harms, values,
and preferences of policymakers, health-care providers and parents, feasibility, and resource
use and whether costs are justifiable relative to benefits in Indian settings.
Each recommendation was graded as strong when there was confidence that the benefits
clearly outweigh the harms, or weak when the benefits probably outweigh the harms, but
there was uncertainty about the trade-offs. A strong or weak recommendation was further
classified as conditional /context specific if the benefits outweigh the harms in some situations
but not in others.
Document review
The GDG met on two occasions and prepared a draft of the full guideline document with
revisions to accurately reflect the deliberations and decisions of the GDG participants. This
draft guideline was then sent electronically to the GDG participants for further comments. The
inputs of the peer reviewers were included in the guideline document and further revisions
were made to the guideline draft as needed. After the peer review process, the revised version
was prepared.

QUESTIONS, EVIDENCE SUMMARIES AND RECOMMENDATIONS
Practice Question 1 : Among preterm neonates born at ≤ 34 weeks’ gestational age and on
any respiratory support, do “higher oxygen saturation targets (91-95%)” compared to “Lower
oxygen saturation targets (85-89%)” affect mortality or severe morbidities?
Characteristics of included studies
We found five RCTs undertaken since 2005 to compare the outcomes of preterm infants
allocated to lower (85–89%) versus higher (91–95%) oxygen saturation targets as part of
prospective individual patient data meta-analysis known as the Neonatal Oxygen Prospective
Meta-Analysis (NeOProM) Collaboration trials.1-7 Results of this metanalysis were used for these
guidelines as we did not find any other eligible RCT published after this large individual
participant data metanalysis. A Cochrane review had synthesized the aggregate data
available from the published reports of these 5 trials.8 In contrast NeOProM meta-analysis results
were derived using raw individual participant data sourced directly from the trial investigators
and combined centrally, making this as the most comprehensive and rigorous analyses
available from these studies data. The methods of the analyses used for the individual
participant data also permitted adjustment for the correlation of multiple births;
standardization of important outcomes across trials, including the definition of major disability;
and enabled testing of the effect of differences in outcome definitions via sensitivity analyses.
Meta-analysis of individual participant data has also provided new insights into the consistency
of results across multiple subgroups that indicate the findings should not be restricted to certain
groups of infants such as those born SGA or at very early gestational ages. Therefore, we used
the NeOProM meta-analysis results for our guidelines. All the studies included in NeOProM
meta-analysis enrolled extremely preterm neonates (gestational age <28 weeks). We used
evidence from NeOProM meta-analysis for making recommendation for preterm neonates ≤34
weeks’ gestational age as there was paucity of evidence in the population of preterm
neonates born between 28 and 34 weeks of gestation. This approach may contribute to
“indirectness” of evidence while making recommendations to neonates born between 28-
and 34-weeks’ gestational age.
Summary of evidence
Table 1a depicts the baseline characteristics of the 5 randomized trials (SUPPORT, COT and
three BOOST II trails) included in the NeOProM meta-analysis. These trials were conducted as
separately funded and managed components of a prospective individual patient data meta-
analysis known as the Neonatal Oxygen Prospective Meta-Analysis (NeOProM) Collaboration.
The trials used Masimo Radical® oximeters (Masimo Corporation, Irvine, Calif., USA). The
intervention in the NeOProM trials was to target SpO2 to the ranges 85% to 89% or 91% to 95%.
Nursing staff delivered the intervention by manually adjusting fraction of inspired oxygen (FiO2)
with the aim of maintaining SpO2 within a desired range. The NeOProM trials were masked
using specially adjusted oximeters so that infants enrolled in both randomization groups were
targeted to the same “displayed” SpO2 range and caregivers were unaware of their group
allocation.
Table 1b shows the GRADE profile summary of evidence on effect of lower (85-89%) vs higher
(91-95%) saturation targets in preterm neonates born at <34 weeks’ gestation age.

Although there was no statistically significant difference between groups in the primary
composite outcome of death or severe neurodevelopmental disability, infants targeted to the
lower SpO2 range had a significantly increased risk of death and of severe necrotizing
enterocolitis (NEC), defined as requiring surgery or causing death. There was no difference
between groups in the risk of severe neurodevelopmental disability. Infants randomized to the
higher target groups had an increased risk of requiring treatment of retinopathy of prematurity
(ROP), but there was no significant difference between the groups in the number of infants
with severe visual impairment. The NeOProM meta-analysis has some limitations. First, all 5 trials
reported less separation in oxygen exposure between treatment groups than anticipated,
largely because the lower SpO2 target groups had higher than intended saturation levels.
Second, 2 trials (BOOST II in United Kingdom and Australia) were stopped early, which may
have resulted in some overestimation of the effect on mortality in these trials. Third, the lack of
an association of SpO2 target range with blindness, but with a clear difference in ROP by
treatment group, may change with longer follow-up, when more visual impairments may
become evident. Fourth, even though the results are generalizable across the 5 trials, caution
should be exercised not to extend these findings to other settings that do not have early
screening and treatment for ROP or skilled nursing care. The trials studied SpO2 target ranges,
not oximeter alarm limits, and these two concepts are not interchangeable. There is lack of
direct evidence in neonates of gestational ages 28-34 weeks with respect to similar critical
outcomes, following use of low/high oxygen saturation targeting during oxygen therapy. It is
to be noted that during the NeOProM trials, infants assigned to low or high oxygen saturation
targets were maintained on same targets, till they reached 36 weeks PMA, even if not receiving
oxygen supplementation.

Table 1a: Summary of studies included in NeOProM Meta-analysis
S. Study name Setting Study Study Intervention Control Outcome Conclusions Limitations of NeOProM
No. and country (level) design Population/ group parameters of meta-analysis
/ LMIC Mean (SD) interest
or HIC gestation/BW
1. Surfactant HIC RCT 1316 preterm Low oxygen High Primary outcome A lower target range 1. All 5 trials reported
Positive neonates saturation oxygen Survival Without BPD of oxygenation (85 to less separation in
Airway between targets saturation and 89%), as compared oxygen exposure
Pressure gestational (85 to 89%) targets Survival Without with a higher range between treatment
and Pulse age of 24 to from birth or (91 to Severe ROP, (91to 95%), did not groups than
Oximetry 27 weeks 6 soon 95%) from IVH, NEC, decrease the anticipated, largely
Trial days. Mean thereafter birth or neurodevelopmental composite outcome because the lower
(SUPPORT)2,3 gestational soon disability at 18-24 of severe ROP SpO2 target groups
USA age was 26±1 thereafter months of age or death, but resulted had higher than
weeks in both in an increase in intended saturation
the groups mortality and a levels.
and mean substantial decrease 2. Two trials (BOOSTII)
Birth weight in severe ROP in United Kingdom
was 836±193g requiring treatment and Australia) were
and 825±193g among survivors. stopped early,
in low and The follow-up study which may have
high showed no significant resulted in some
saturation differences in later overestimation of
target group disabilities between the effect on
respectively. the groups. mortality in these
2. Canadian HIC RCT 1201 Preterm Low oxygen High Primary outcome: Lower oxygen trials.
Oxygen neonates saturation oxygen Rate of death or saturations 3. The lack of an
Trial4 (COT), between targets saturation disability at 18 compared with higher association of SpO2
Canada gestational (85 to 89%) targets months. Secondary saturations had no target range on
age 24 weeks from birth or (91 to outcomes; ROP, significant effect on blindness, but with a
to 27 weeks 6 soon 95%) from brain injury, PDA, the rate of death or clear difference on
days. Mean thereafter birth or NEC, disability at 18 months. ROP by treatment
gestation was soon BPD, and the Targeting lower group, may change
25.6± 1.2 thereafter duration of use of compared with higher with longer follow-
weeks in both positive airway saturations reduced up, when less severe
groups and pressure and the mean PMA at last visual impairments
mean Birth supplemental use of oxygen therapy may become
weight was oxygen from 36.2 to 35.4 apparent.
829± 188 g weeks (mean

and 845 ± 197 difference adjusted 4. Even though the

g in low and for center, -0.8; 95% results are
high CI, -1.5 to -0.1; P=.03) generalizable across
saturation but had no significant the 5 trials, caution
target group effect on any other should be exercised
respectively. outcomes, not to extend these
3. Benefits of HIC RCT 2448 preterm Low oxygen High Primary outcome: Targeting lower findings to other
Oxygen infants born saturation oxygen disability-free survival oxygen saturation settings that do not
Saturation between targets saturation at 2 years was associated with have early
Targeting gestational (85 to 89%) targets Secondary outcome an increased risk of screening for ROP,
(BOOST) II age of 24 from birth or (91 to ROP, IVH, death and NEC and appropriate ROP
Trial5,-7, 03 weeks soon 95%) from NEC, reduced rate of ROP. treatment, or skilled
trials one to 27 weeks 6 thereafter birth or BPD/ oxygen There were no nursing care
each from days. were soon requirement at 36 significant between regarding alarm
United enrolled in the thereafter weeks of group differences in limits.
Kingdom, three postmenstrual age, rates of other
Australian, trials (973 in PDA, outcomes or adverse
and New the United events.
Zealand Kingdom,
1135 in
Australia,
and 340 in
New
Zealand).
Mean
gestational
age was 26±1
week in both
the groups
and mean
Birth weight
range of the
study subjects
was between
817±177g and
884±186 g in
the three
trials.
BPD: Bronchopulmonary dysplasia, HIC: high income countries, IVH: Intraventricular hemorrhage, NEC: necrotizing enterocolitis, PDA: Patent ductus arteriosus, RCT: Randomized
controlled trial, ROP: retinopathy of prematurity

Table 1b: Summary of evidence table
Low saturation threshold compared to high saturation threshold for preterm infants <34 weeks of
gestational age and requiring oxygen support
Patient or population: Preterm <34 weeks of gestation and requiring oxygen support
Setting: Health care settings caring for preterm infants
Intervention: Low saturation targets (85-89%)
Comparison: High saturation targets (91-95%)
Outcomes Anticipated absolute effects* Relative effect № of Certainty of
(95% CI) (95% CI) participants the evidence
Risk with high Risk with Low (studies) (GRADE)
saturation saturation
threshold threshold
Major disability 383 per 1,000 387 per 1,000 RR 1.01 3867 ⨁⨁⨁⨁
by 18 to 24 (356 to 417) (0.93 to 1.09) (5 RCTs) HIGH
months of
corrected age
Death before 160 per 1,000 186 per 1,000 RR 1.16 4958 ⨁⨁⨁⨁
discharge (165 to 210) (1.03 to 1.31) (5 RCTs) HIGH
Severe 148 per 1,000 106 per 1,000 RR 0.72 4089 ⨁⨁⨁⨁
retinopathy of (90 to 125) (0.61 to 0.85) (5 RCTs) HIGH
prematurity or
retinal therapy
(trialist defined)
Severe 90 per 1,000 112 per 1,000 RR 1.24 4929 ⨁⨁⨁⨁

Necrotizing (95 to 133) (1.05 to 1.47) (5 RCTs) HIGH
enterocolitis
(Severe NEC)a
Supplemental 442 per 1,000 384 per 1,000 RR 0.87 4175 ⨁⨁⨁⨁
oxygen (358 to 415) (0.81 to 0.94) (5 RCTs) HIGH
requirement at
36 weeks
postmenstrual
age
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in
the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio
Explanations: a. Treated with surgery or leading to death during initial hospitalization
Summary of judgements
Balance of benefits and harms: Individual patient data meta-analysis of NeOProM trials
showed high-certainty evidence of an increase in the risk of mortality during the initial hospital
stay (RR 1.16; 95% CI: 1.03 to 1.31) and of severe NEC (RR 1.24; 95% CI: 1.05 to 1.47) in the group
randomized to the lower oxygen saturation targets (85-89%) compared to higher oxygen
saturation targets (91-95%). There was no difference in the risk of major neurodevelopmental
disability by 18 to 24 months of corrected age (RR 1.01; 95% CI: 0.93 to 1.09). There is high
certainty evidence demonstrating a reduction in the risk of severe ROP (RR 0.72; 95% CI: 0.61
to 0.85) and the rate of BPD (RR 0.87; 95% CI: 0.81 to 0.94) with the use of lower oxygen
saturation targets (85-89%) compared to higher oxygen saturation targets (91-95%). However,
ROP treatment was successful in these studies and no long-term difference was reported in the
incidence of severe visual impairment at 18-24 months of corrected age. As already discussed,

due to paucity of evidence from high quality RCTs among neonates born between 28 and 34
weeks of gestational age, we used the above studies to draw recommendations for this
gestational age group also. The GDG felt that this is a reasonable approach considering the
similar predisposition to morbidities such as ROP – yet the certainty of evidence in the group of
neonates born at gestational ages between 28 and 34 weeks is Moderate due to
downgrading for indirectness of evidence.
Values and preferences: The serious harms of lower saturation targets (increased mortality
before hospital discharge and NEC requiring surgery) outweigh the benefit of reduced risk of
ROP requiring treatment and BPD. Moreover, ROP treatment was successful and there was no
long-term difference in incidence of severe visual impairment at 18-24 months of corrected
age. The trials included in the meta-analysis took place in a developed world setting where
SpO2 monitoring is universally available and ROP screening and treatment is well established
in the care protocol of these preterm babies. All health care workers involved in care of
preterm needs to be aware of the need for timely screening and treatment of ROP. Since
mortality before discharge and long-term problems of operated NEC are of serious concern
for health care providers, policymakers, and parents are more likely to give a high value to the
benefits of using higher as compared to lower oxygen saturations.
Costs: There is no difference in the cost of implementing a policy of higher as compared to

lower oxygen saturation targeting as both will require a good quality reliable pulse oximeter,
compressed medical air and air-oxygen blender. However, need to target higher oxygen
saturation may delay stopping oxygen therapy and therefore prolong the hospital stay.
RECOMMENDATION
1. All preterm neonates born at ≤ 34 weeks of gestational age and requiring

respiratory support should be managed using oxygen saturation target of 91-95%
in preference to lower (85-89%) oxygen saturation targets.
Strong recommendation
High certainty of evidence for less than 28weeks’ gestational age and Moderate
certainty of evidence for 28-34 weeks’ gestational age
Justification: Strong recommendation, based on evidence of high certainty demonstrating

reductions in the risk of mortality (critical outcome) and of severe NEC before discharge
(important outcome) with no significant effect on the long term visual and
neurodevelopmental outcomes among extremely preterm neonates (< 28 weeks’ gestation).
For neonates born between 28 and 34 weeks, the GDG makes a strong recommendation
based on moderate certainty of evidence for similar outcomes.
Note: There is a small but significant increase in the risk of ROP requiring treatment with use of
higher oxygen saturations targets. For every 1000 babies treated with higher oxygen saturation
targets (91-95%), there may be 42 additional cases of severe ROP requiring treatment but there

may be 26 fewer deaths before discharge. Facilities to implement a strict protocol for timely
screening and early treatment of ROP must be present wherever preterm neonates are
administered oxygen and the guideline is implemented.
Practice Question 2: Among neonates born at > 34 weeks of gestational age and on any
respiratory support, do “higher saturation targets (91-95%)” as compared to “lower saturation
targets (85-89%)” affect mortality and severe morbidities?
Summary of evidence
Guideline addressing this question could not be graded as we did not find any RCT or
observational study directly comparing the different oxygen saturations among the late
preterm and term newborns requiring oxygen therapy. Observational studies on SpO2 trends
among healthy preterm and term neonates during first few days of life after birth have shown
that after an initial increase in SpO2 to >90% during the first few minutes of age, SpO2 stabilizes
over next 20 to 24 h to 97 to 98%, with the normal range from 94 to 100%.9-12 Prospective cohort
study of SpO2 measurement over 6 h during 12 to 48 h of birth on 20 late-preterm (35 to 36
weeks of gestation) and 40 term infants breathing room air revealed that these newborns
spend approximately only 7% of the time at SpO2 ⩽90% and this time decreased as gestational
age and birth weight increased.13
There is indirect evidence from experimental animal data and studies on young infants that
use of excess oxygen at the time after birth is associated with increased oxidative stress and
poor outcome. In lambs with PPHN induced by prenatal ligation of the ductus arteriosus, SpO2
in the 90–97% range resulted in lowest pulmonary vascular resistance.14 Current evidence
suggests that SpO2 range 90%–95% is safe in term infants with hypoxic respiratory failure and
persistent hypertension of the newborn.15 Among neonates born at ≥36 weeks of gestation and
with severe perinatal acidemia hyperoxia (arterial PO2 > 100 mm Hg) during first hours of life is
associated with higher incidence of hypoxic-ischemic encephalopathy (HIE) than those
without hyperoxia (58% vs 27%; P = 0.003). Among neonates who developed HIE, admission
hyperoxia was found be associated with higher incidence of abnormal brain magnetic
resonance imaging findings.16
A multi-center randomized study on infants with bronchiolitis comparing target SpO2 of ≥90%
and ≥94% has demonstrated that infants who were maintained at a SpO2 closer to 90% had
less need for oxygen supplementation (56% versus 73%), a lower duration of oxygen use (5.7 h
versus 27.6 h), and an earlier discharge from the hospital (40.9 h vs. 50.9 h).17 Infants managed
with the lower target of 90% also regained satisfactory feeding sooner and had fewer
readmissions to hospital over next 28 days. A large, randomized trial involving adult patients
who were expected to require intensive care for >72 h compared effect of oxygen therapy to
maintain PaO2 between 70 and 100 mm of Hg (SpO2 between 94% and 98%) with PaO2 values

up to 150 mm Hg (SpO2 values between 97% and 100%). Patients who were maintained at the
lower oxygen range had lower risk of mortality, shock, liver failure, and bacteremia.18
Balance of benefits and harms
Based on animal experimental data and indirect evidence from older group of patients it is
clear that hyperoxia is deleterious at all stages of life and is associated with poor outcome.
Although neonates are different from infants and adults, from a physiological standpoint there
seems to be similarities in oxygen saturation targets across all age groups. Available evidence
supports maintaining SpO2 in the range of 91-95% (arterial PO2 50–80 mm Hg) will avoid
deleterious effects of both hypoxemia and hyperoxia in late preterm and term infants on
oxygen therapy.
RECOMMENDATION
2. All neonates born at >34 weeks of gestational age and requiring respiratory
support may be managed using oxygen saturation targets of 91-95% in preference
to lower (85-89%) oxygen saturation targets.
Weak recommendation, Not graded
Practice Question 3: Among preterm neonates born at <37 weeks of gestational age and with
established/evolving bronchopulmonary dysplasia, do “standard saturation targets (91-95%)”
compared to “higher saturation targets (95-98%)” affect mortality or severe morbidities?
Table 2a depicts the baseline characteristics of the 2 randomized trials (STOP-ROP and BOOST
I trails)20,21 which are included in the evidence profile. Both RCTs compared risk of ROP between
standard vs high oxygen saturation targeting in preterm infants with evolving or established
BPD. The target SpO2 varied between the studies with 89% being the lowest and 99% the
highest value. One RCT also compared developmental and growth at 1 year corrected
gestational age. Overall, the population size was large. An RCT named bronchopulmonary
dysplasia saturation targeting (BPD Star) is in progress.

Table 2a: Summary of studies – standard versus high oxygen saturation targets in established or evolving bronchopulmonary dysplasia
Sr. Study name Study Study Intervention Control Outcome Conclusions

N and country design Population/ group parameters of
o. Mean (SD) gestation/BW interest
1. Supplemental Multicentric 649 High oxygen Standard Primary outcome Use of supplemental oxygen at pulse oximetry
Therapeutic RCT Preterm neonates with pre- saturation oxygen saturations of 96% to 99% did not cause
Oxygen for threshold ROP in at least 1 eye targets saturation Eyes confirmed additional progression of pre-threshold ROP but
pre-threshold Mean gestational age was (96 to 99%) for targets to have reached also did not significantly reduce the number of
Retinopathy of 25.4±1.5 weeks in both the at least 2 (89 to 94%) threshold ROP
Prematurity groups weeks for at least infants requiring peripheral ablative surgery.
and referred for
(STOP-ROP) Mean PMA at entry was 2 weeks cryotherapy or
USA 35.3±2.6 and 35.4±2.5 weeks laser therapy Supplemental oxygen increased the risk of
Mean birth weight was adverse pulmonary events including pneumonia
721±160 g and 731±161 g. and/or exacerbations of chronic lung disease
Mean wt. at entry was
and the need for oxygen, diuretics, and
1538±445 g and 1556±442 g in
standard and high saturation hospitalization at 3 months of corrected age.
target group respectively.
2. Oxygen- Multicentric 358 preterm neonates born High oxygen Standard Growth and Targeting a higher oxygen-saturation range in
Saturation RCT <30 weeks of gestation and saturation oxygen major extremely preterm infants who were dependent
Targets and who remained dependent on targets saturation developmental on supplemental oxygen conferred no significant
Outcomes in supplemental oxygen (95 to 98 %) targets abnormality at 1
benefit with respect to growth and development
Extremely (delivered by any method (91 to 94%) years of age
and at any level) at 32 weeks and resulted in an increased burden on health
Preterm Infants
of postmenstrual age Secondary services
BOOST I trial outcome
Mean gestational age were Duration of
26.6±1.7 and 26.5±1.6 weeks oxygen therapy,
Australia
Mean Birth weight was the duration of
918±299 g and 916±231g in assisted
standard and high saturation ventilation and of
target group respectively. the hospital stay,
and the
frequency of
home- based
oxygen therapy.

Summary of evidence
Table 2b shows the GRADE profile summary of evidence on effect of standard (91-95%) vs
higher (96-98%) saturation targets in preterm neonates born at <37 weeks of gestation age.
Some benefit in preventing ROP is at the cost of increased duration of oxygen requirement
and hospitalization. The evidence was judged to be of high certainty as included studies were
well conducted RCTs with adequate sample size and a low risk of bias.
High saturation (95- 98%) threshold compared to standard (91-95%) saturation threshold for preterm
infants with evolving or established BPD
Patient or population: Preterm infants with evolving or established BPD

Setting: health care facility caring for preterm
Intervention: high saturation(95- 98%) threshold
Comparison: standard(90-94%) saturation threshold
Anticipated absolute
effects*(95% CI)
Certainty of
Relative
Risk with Risk with № of participants the evidence
Outcomes effect
standard high (studies) (GRADE)
(95% CI)
(89-94%) saturation
saturation (95- 98%)
threshold threshold
Neurodevelopmental
outcome at 1 year 231 per
assessed with: major 1,000
neurosensory (159 to
disability defined as 342) RR 0.96
241 per 334 ⨁⨁⨁⨁
cerebral palsy, (0.66 to
1,000 (1 RCT) HIGHa,b
blindness, and Griffith 1.42)
score less than 2SD
below mean
follow up: mean 1
year
293 per
RR 0.81
Development of ROP 363 per 1,000 954 ⨁⨁⨁⨁
(0.67 to
requiring treatment 1,000 (245 to (2 RCTs) HIGH
0.97)
351)
265 per
OR 1.78
Home oxygen 169 per 1,000 358 ⨁⨁⨁⨁
(1.20 to
therapy 1,000 (196 to (1 RCT) HIGH
2.64)
349)
Requirement of 61 per RR 0.54

112 per 358 ⨁⨁◯◯
ablative retinal 1,000 (0.27 to
1,000 (1 RCT) LOWc
surgery (30 to 124) 1.10)
407 per
RR 1.36
Prolonged oxygen 300 per 1,000 1007 ⨁⨁⨁⨁
(1.14 to
therapy 1,000 (343 to (2 RCTs) HIGHa
1.6)
482)

High saturation (95- 98%) threshold compared to standard (91-95%) saturation threshold for preterm
infants with evolving or established BPD
Patient or population: Preterm infants with evolving or established BPD

Setting: health care facility caring for preterm
Intervention: high saturation(95- 98%) threshold
Comparison: standard(90-94%) saturation threshold
effects*(95% CI)
Certainty of
Relative
Risk with Risk with № of participants the evidence
Outcomes effect
standard high (studies) (GRADE)
(95% CI)
(89-94%) saturation
saturation (95- 98%)
threshold threshold
Remained 126 per

RR 1.86
hospitalized at 3 68 per 1,000 649 ⨁⨁⨁◯
(1.14 to ,
months of corrected 1,000 (77 to 207) (1 RCT) MODERATEa b
3.06)
age
36 per RR 1.49
24 per 1008 ⨁⨁⨁◯
Mortality 1,000 (0.72 to
1,000 (2 RCTs) MODERATEd
(17 to 73) 3.06)
BPD 645 per

assessed with: 1,000 RR 1.40
461 per 358 ⨁⨁◯◯
OXYGEN (530 to (1.15 to
1,000 (1 RCT) LOWc
REQUIREMENT AT 36 783) 1.70)
WEEKS PMA
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the
comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio; OR: Odds ratio

Explanations
A. Only one RCT
B. Follow up was only 1yr only. It is too short to assess long term minor neurodevelopment outcome
C. Secondary outcome
D Downgraded in view of imprecision – confidence intervals are crossing clinical thresholds of treatment change
Balance of benefits and harms: Available evidence of high certainty shows that higher versus
standard oxygen saturations did not offer any benefits in the critical outcome of
neurodevelopmental outcome at corrected age of 12 months (RR: 0.96; 95% CI: 0.66-1.42) and
evidence of moderate certainty shows no difference in the other critical outcome of mortality
(RR: 1.49; 95% CI: 0.72-3.06). High certainty evidence also shows that higher oxygen saturations
targets may be associated with a lower risk of ROP requiring treatment (RR 0.81; 95% CI: 0.67
to 0.97) but worsened the risk of adverse pulmonary outcomes such as the need for home
oxygen and prolonged oxygen therapy. There is moderate certainty evidence to show that
higher oxygen saturations targets may be associated with the need for prolonged
hospitalization (RR 1.14; 95% CI: 1.14-3.06).
Values and preferences: Based on evidence available, there was no significant difference in
mortality and neurodevelopmental outcome at 1 years of age with standard versus higher

oxygen saturations in neonates with BPD. Rather, higher saturation targets are associated with
increased duration of hospitalization and prolonged requirement of oxygen therapy. Health
care providers, policymakers, and parents are likely to give a higher value to the harm of
adverse pulmonary outcomes of using higher oxygen saturations as compared to standard
oxygen saturations.
Costs: Higher saturation targeting (95-98%) is likely to be associated with higher cost of
treatment due to longer duration of hospital stay as well as prolonged use of oxygen.
RECOMMENDATION
3. All neonates with evolving / established BPD and requiring respiratory support
should be managed using oxygen saturation targets of 91-95% in preference to
higher (95-98%) oxygen saturation targets.
Strong recommendation, High certainty of evidence
Justification : Strong recommendation, based on high certainty evidence of significant

increase in the risk of BPD (critical outcome) as well as other adverse pulmonary outcomes
with evidence of no benefit or harm with respect to critical outcomes of mortality or major
neurological disability at 1 year of age. Higher saturation targets are likely to increase
duration of hospitalization and cost of treatment.
Practice Question 4 : Among neonates born at ≥ 34 weeks of gestational age and with mild
respiratory distress, does “oxygen by hood or oxygen by incubator” compared to “oxygen by
nasal cannula” affect mortality or severe morbidities?
In infants treated with oxygen via nasal cannula, the approximate effective hypopharyngeal
fraction of inspired oxygen (FiO2) can be calculated using formulae incorporating FiO2,
cannula flow, and minute ventilation. Standardized charts based on infant weight, set FiO2,
and cannula flow have been validated to determine a relatively accurate estimation of the
effective FiO2. However, effective oxygen concentration can be influenced by nasal versus
mouth breathing as well as breathing rate, volume, and inspiratory time which fluctuate over
time. 22
Oxygen hoods (oxyhood or headbox) that are commonly used also maintain a set oxygen
environment but are not servo-controlled.
Limited humidification by the nasal cannula therapy may result in drying of the upper airway
mucosa, which can contribute to nasal mucosal injury and increased risk of infections.

We identified two studies comparing oxygen delivered by hood oxygen or oxygen rich
environment with nasal cannula (Table 3 a).
Summary of evidence
Table 3 b shows the SoF table – There was no difference between both techniques in episodes
of intermittent hypoxia: [Incubator oxygen group: mean, SD:117 ± 77, nasal cannula group:
mean, SD: 130 ± 63; MD [95% CI] : 13.00 [-24.53, 50.53]]. This contrasted with the findings
mentioned in the study itself which found that episodes of intermittent hypoxia as well as severe
hypoxia were significantly lower in the environmental oxygen group when compared to nasal
cannula. 22 No difference in proportion of time with SpO2 91-95%, and > 95% and number of
bradycardia episodes or episodes of severe intermittent hypoxia. None of the critical
outcomes such as mortality, BPD or ROP were reported.

Table 3a: Studies comparing modes of oxygen administration in neonates
Study Design Population Methodology Intervention Control Outcome Conclusion Comments

Travers et Randomized 27 Preterm Infants Supplemental Supplemental Primary In preterm Blinding of
al.22 cross over trial infants < 37 randomized to oxygen via oxygen via outcome - infants intervention
Birmingham, Comparison of weeks, needing two interventions oxygen nasal cannula Number of receiving not possible.
USA oxygen oxygen via nasal for 24 hours and environment with low flow episodes of supplemental Computer
environment cannula at < then crossed over maintained by rates (≤1.0 L per intermittent oxygen, servo- recording
with nasal 1L/kg/min for another 24 a servo- kg per minute) hypoxia controlled not visible to
cannula hours. 15-30 controlled (SpO2 < 85% oxygen caregivers
oxygen minutes washout system used for ≥ 10 environment
period between servo control of seconds) per and nasal
crossover to oxygen delivery 24 hours. cannula are
allow and standard Secondary similar with
stabilization. binasal nasal outcomes- respect to the
Crossover was prongs were Number of number of
performed every used in the episodes of episodes of
24 hours till the other group severe intermittent
infant did not intermittent hypoxia
need oxygen. hypoxia
Effective FiO2 was (SpO2 < 80%
calculated using ≥ 10
standardized seconds) per
charts based on 24 hours.
weight, FiO2 and
flow rate and Proportion of
was maintained time with
while swapping. SpO2 < 85, <
Data collected 91%,between
using iX Trend 91-95% and >
software. 95%
Number of
bradycardia
episodes

Yllescas- Comparative, Clinically stable Clinically stable Supplementary Supplementary Failure of Nasal prongs Article in
Medrano prospective, preterm infants preterm infants oxygen by nasal oxygen by oxygen were more Spanish, not
Eucario et longitudinal, (<37 weeks of with normal prongs oxygen hood support effective to indexed in
al.23 and analytical gestation) blood gases & leading to avoid failure in MEDLINE
Spain study requiring requiring escalation of the retirement
respiratory respiratory respiratory of the phase II
support after support after support of respiratory
retirement from retirement from support, but
nasal CPAP or nasal CPAP or they were
nasopharyngeal nasopharyngeal associated
ventilation ventilation were with an
(phase II given increment in
respiratory supplementary the frequency
support) oxygen by nasal of nasal
prongs (n=33) or lesions.
oxygen hood
(n=34). They were
under
observation for
detection of
apnea or
worsening
respiratory status.

Table 3 B: Summary of findings: Environmental oxygen versus oxygen by nasal cannula

Nasal cannula compared to closed (hood box, incubator) oxygen delivery system for
neonates > 34 weeks with mild respiratory distress
Patient or population: neonates > 34 weeks with mild respiratory distress
Setting:
Intervention: Nasal cannula
Comparison: closed (hood box, incubator) oxygen delivery system
Anticipated absolute effects*
(95% CI)
Certainty of
Risk with closed Risk with Nasal Relative № of
the Comment
Outcomes (hood box, cannula effect participants
evidence s
incubator) (95% CI) (studies)
(GRADE)
oxygen delivery
system
Episodes of MD 13 higher
intermittent (24.53 lower to
hypoxia The mean 50.53 higher)
⨁⨁⨁◯
assessed episodes of 54
-
with iX trend intermittent (1 RCT)
MODERATEa
software for hypoxia were 0
multipara
monitors
Episodes of MD 0.02 higher
severe (0.51 lower to
intermittent The mean 0.56 higher)
hypoxia episodes of ⨁⨁⨁◯
54
assessed severe -
(1 RCT)
with iX trend intermittent MODERATEa
software for hypoxia were 0
multipara
monitors
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group
and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; MD: Mean difference
a Downgraded in view of imprecision – confidence intervals are crossing clinical thresholds of treatment change
Benefits versus harms: The only RCT by Travers observed that use of servo-controlled oxygen
environment as well as nasal cannula oxygen was associated with similar number of episodes
of intermittent and severe intermittent hypoxemia in every 24 hours of observation. There is no
statistically significant difference in the number of episodes of bradycardia and requirement
of recorded bedside interventions. The study does not report any difference in other critical
outcomes such as mortality or bronchopulmonary dysplasia. The World Health recommends
the use of nasal cannula with flow of 0.5-1 L/mt as the preferred mode of oxygen administration
in neonates. This is based on the most optimal combination of safety, efficacy, and efficiency
with nasal cannula compared to other modes. Hood oxygen use especially with inadequate
flows and tight seal can be associated with the risk of carbon dioxide toxicity as well as
wastage of oxygen. It may be difficult to ascertain the precise concentration of oxygen (FiO2)
with hood oxygen use without an oxygen analyser.24 Oxygen via nasal cannula also helps in
promoting parent-baby interaction, Kangaroo mother care (KMC) and breast feeding

Values and preferences
The caregivers may prefer nasal cannula delivery system since it is easy to fit, comfortable for
use and does not interfere with parent-baby interactions, Kangaroo mother care (KMC) and
breast feeding.
Cost
A quality improvement initiative to rationalize and reduce the use of oxygen in the SNCU of
Sehore, Madhya Pradesh, India found that using nasal prongs at a flow rate of 0.5-1 L/mt
reduced the cost of treatment up to Rs 295/- per neonate when compared to use of hood
oxygen with flow of 4-6 L/mt. During the study period, the total expenditure for refilling of
oxygen cylinders decreased from 79% of the maintenance budget to 38% during the
sustenance phase of the study. A nearly 50% relative reduction in cost is possible with the use
of nasal prongs over hood oxygen merely due to lower oxygen consumption without
accounting for the cost saved on procuring oxygen hoods.25
RECOMMENDATION
4. In neonates born at >34 weeks of gestation and with mild respiratory distress,
nasal cannula with low flow rate (0.5-1 L/min) should be used for delivering oxygen
in preference to oxygen by hood or incubator oxygen.
Strong recommendation, Moderate certainty of evidence
Justification: Strong recommendation, based on based on moderate certainty of evidence

on similar incidence of bradycardia and significant interventions to improve oxygenation and
higher value and preference of caregivers for nasal cannula due to ease of use, lower cost,
lower oxygen wastage, lower risk of CO2 toxicity and comfort with the use of nasal cannula to
deliver oxygen.

Practice Question 5 : Among neonates on oxygen support by nasal cannula (low/ high flow),
does “humidification” compared to “no humidification” affect mortality or severe morbidities?
Background
In neonates <1 L/min flow is usually considered low flow. Low flow oxygen may result in room
air being entrained with the oxygen, diluting the FiO2 and contributing the additional humidity
from room air26-27. Among adults, the natural humidification mechanism of upper airway has
been shown to be adequate in humidifying inhaled oxygen when the patient is on low flow
oxygen therapy.28-29
In practice low flow oxygen is commonly humidified using non-heated bubble humidifier. It has
been shown that the bacterial contamination of bubble humidifier bottle is common, and it is
up to 54% after 24 h use.30-31 Findings from a meta-analysis among adult population indicate
that non-humidified and humidified oxygen in low-flow oxygen administration provide no
differences on dry nose, dry nose and throat, nosebleed, chest discomfort, smell of oxygen
and SpO2 after oxygen administration.
On the other hand, high flow oxygen cannula delivers the neonate’s entire ventilatory
demand, meeting, or exceeding the neonate’s peak inspiratory flow rate. The environmental
air dose not contributes to the inhaled gas mixture. The natural humidification system is not
adequate in humidifying the inhaled gas mixture during high flow oxygen therapy.
Summary of evidence
We did not find any RCT or observational study comparing humidified and non-humidified
oxygen administration among neonates requiring oxygen therapy. Following table summarizes
the guidelines from world health organization (WHO).24
Table 4: Summary of WHO guidelines about humidification of inspired gases during oxygen
therapy
Recommendation Quality of evidence
1 When oxygen is delivered at a standard flow rate Strong recommendation

(0.5–1L/min) for a neonate through a nasal (low-quality evidence)
catheter or nasal prongs, humidification is not
necessary.
2 When oxygen is delivered at a higher than the Strong recommendation
standard flow rate (>1 L/min) through a nasal (low-quality evidence)
catheter or nasal prongs, humidification is
necessary.
Values and preferences: Caregivers are likely to give a high preference to the advantages of
humification at higher flows (> 1 L/min) as this is beyond the capacity of the newborn’s nasal
mucosa to normally humidify. The physiological advantages of humidification such as
avoidance of drying and desiccation, reduction in metabolic work of breathing, avoidance
of infections, prevention of lung atelectasis etc. are attractive.

Cost: Heated humidifiers are more effective than bubble chambers or flow meters filled with
cold water; however, they are expensive (Rs 2.5-3 lakhs per unit) and require a continuous
power supply.
RECOMMENDATION
5. In neonates being administered oxygen at high flow rate (>1 L/min) through
nasal cannula, warming and humidification of the inhaled gases may be preferred
over no warming and humidification.
Warming and humidification may not be necessary when flow rate through nasal
cannula is low (< 1 L/min).
Weak recommendation, Not graded
Practice Question 6: Among neonates on any respiratory support, does “intermittent

monitoring of oxygen saturation” compared to “continuous monitoring of oxygen saturation”
affect mortality or severe morbidities?
Summary of evidence
We did not find any RCT or any observational study that compared intermittent saturation
monitoring with continuous monitoring in neonates on respiratory support. We did not find any
systematic review addressing this concern. As per the WHO document on use of oxygen
therapy in children, administration of oxygen therapy should be guided by pulse oximetry,
when available. The document did not specify whether to use it continuously or intermittently.24
In an observational study aiming to evaluate the effectiveness of intermittent pulse oximetry in

a low resource setting, neonates requiring oxygen therapy were evaluated with intermittent
SpO2 monitoring while they were on concealed continuous pulse oximetry. Preterm neonates
on respiratory support spent only 15.7% time (95% confidence intervals [CI]: 13.3-18.8%) within
the saturation target range with intermittent pulse oximetry performed an average of 4.7 times
a day. The same group spent 75% (95% CI: 63.6 – 81.1%) time above the saturation target.32
RECOMMENDATION
6. In neonates on any respiratory support, oxygen saturation may be monitored

continuously in preference to intermittent monitoring.
Strong recommendation, Not graded

Justification : Despite the paucity of evidence, the group members recommend continuous
pulse oximetry monitoring in neonates on any respiratory support. This has been extrapolated
from the evidence in very preterm infants where they spent most of the time in hyperoxia.
Strong recommendation is based on the confidence that the possible desirable effects on
lowering the risk of hypoxia, hyperoxia and the resultant effect on critical outcomes such as
mortality, BPD and ROP are likely to outweigh the harms as well as the increased demand on
resources. The continuous monitoring of oxygen saturations is likely to be preferred by
caregivers and parents due to the above benefits. Not graded due to lack of evidence and
is based consensus among experts.
Practice Question 7 : Among neonates on any respiratory support, does use of “pulse oximeter
with SET technology” compared to “pulse oximeter with non-SET technology” affect mortality
or severe morbidities?
Background
Continuous monitoring by pulse oximetry is the standard of care among preterm and critically
ill newborn in the neonatal intensive care unit (NICU). It has also been recommended in the
delivery room. The goal of oxygen therapy is to prevent hypoxia and hyperoxia because both
can have detrimental effects on the health of the newborn. To achieve this goal, care
providers must accurately recognize the need for oxygen in the newborn after birth and adjust
the fraction of inspired oxygen (FiO2) as needed while simultaneously ensuring adequate
ventilation. Hence, an ideal pulse oximeter should be able to pick up saturation signals fast,
should accurately identify hypoxemia and avoid false positive alarms. Though the outcome
variables were not originally listed, we included them in the analysis on post-hoc basis since
these are important considerations while choosing a pulse oximeter.
We identified 7 studies comparing SET technology vs standard pulse oximetry.33-39 All the studies
enrolled small number of neonates. The studied population had heterogeneity with respect to
the gestational age and severity of respiratory status as indicated by the requirement for
respiratory support as well as setting – such as delivery room versus neonates in NICU. However,
all the studies are well designed high-quality prospective studies. The search strategy is
described in table 7 in appendices.
Table 5A shows characteristics of the included studies while table 5B shows the summary of
findings.

Table 5 A: Studies evaluating use of pulse oximeter with signal extraction technology33-39
Study, Design, Place Population Intervention Outcomes Study description

Objective
Hay 2002 26 Neonates Comparison of False alarm rate Sensors were attached to different feet for 3 hours
Denver Colorado, USA BW 900-2710 grams Masimo SET with Drop out alarm and then switched for another 3 hours
To compare the Needing supplemental Nellcor N-200, True bradycardia Blinded study designs (only the alarms were active
performance of Masimo SET oxygen or mechanical Nellcor N-395, and research nurse did not participate in patient
with Nellcor N-200, Nellcor ventilation Novametrix MARS care.
N-395, Novametrix MARS NICU setting and Philips Viridia 156 hours of monitoring
and Philips Viridia Heart rate
Pulse oximeters corroboration with
Datascope
passport monitor
(Parasmus, NJ)
Workie 2005 36 Neonates (15 Masimo SET False alarm rate Sensors placed on different limbs in same patient
Washington, USA ventilated, 3 nCPAP, 2 compared with Patients were randomly assigned for digit selection
Objective- Comparison of nasal cannula oxygen, 1 Philips Fourier True alarm rate 2-hour recording on each patient
efficacy of Masimo SET tracheostomy with Artifact
with Philips Fourier Artifact oxygen, 14 receiving Suppression Number of dropouts 70 hours of monitoring
Suppression technology room air technology (FAST)
(FAST) pulse oximeter Mean GA 32 weeks pulse oximeter Duration of dropouts
(range 24-42)
Mean chronological age Heart rate from
18 days (SD 16 ) pulse oximeter
correlated with
ECG heart rate
Jeyapal 2016 150 Term AGA neonates Masimo SET Time for reliable Probe from each pulse oximeter were attached to
Pondicherry in delivery room not compared with saturation reading palm or wrist of right upper limb simultaneously.
India needing resuscitation. Nellcor oxima Probe placements to wrist or palm were block
Objective – To compare Median BW 3100 g N600x pulse randomized
performance of 2 different (2760-3380 g) oximeter Sequential saturation values were recorded every
pulse oximeters in neonatal minute till 10 minutes of life.
transition

Nizami 2015 11 preterm infants Masimo SET False alarm rate Simultaneous monitoring on each foot. The probes
Ottawa, Canada BW in grams, Median compared with were switched midway through the study.
Objective- To compare (range) 1197 (515-2240) Nellcor Oximax True alarm rate Selection of limb was randomized prior to study.
data characteristics and GA, median (range) 28 pulse oximeter. 4-hour recording on each patient.
performance of Masimo SET (25-35) weeks Sensitivity
with Nellcor Oximax pulse The ECG heart Research and clinical care team were different
oximeter. rate from Infinity PPV
Delta monitor was
collected to Accuracy
corroborate pulse
oximeter’s pulse
rate.
Pinnamaneni 2010 40 Stable infants in NICU Masimo radical Time taken for oximeter Oximeter attached to right wrist and allocation
Dublin, Ireland or postnatal ward compared with to display data. was done in random manner
Objective – To determine BW, (Median, IQR) 2390, Nellcor N 595
how quickly data can be 1465-3263 grams pulse oximeter
obtained using Masimo or GA (Median, IQR) 36
Nellcor pulse oximeter in (36-40) weeks
delivery room
Dawson 2013 44 term or near-term Masimo SET Mean difference Simultaneous recording on each foot
Melbourne, Australia infants delivered by radical compared between HR measured Data collected for 10 mins
Aim – To compare heart elective caesarean to Nellcor Oximax by ECG and HR
rate measurements from section. Study place – N 600x measured by pulse Research and clinical teams were different
Masimo and Nellcor pulse Delivery room ECG recorded oximeter
oximeters against heart rate GA, mean (SD) – 38 (1) with Philips Agilent
measured via 3 lead ECG. weeks M3 monitor
BW, mean (SD)- 3246
(527) grams
Sahni 2002 15 healthy term infants Masimo SET Drop out duration at Simultaneous recording on left foot. Optical
New York USA undergoing circumcision compared with baseline, during and shielding of sensors
Aim – To compare the BW, mean (SD) – 3408 Nellcor N 200 after circumcision. Baseline data collection for 10 minutes and then
effects of motion on (458) grams pulse oximeter during and after circumcision for total duration of 1
measurements of SpO2 and HR monitored with hour
HR made with Masimo and Hewlett Packard
Nellcor pulse oximeters 3680 monitor

Table 5 B: SUMMARY OF FINDINGS
SET technology pulse oximetry compared to standard pulse oximetry for preterm and term infants
needing oxygen therapy
Patient or population: preterm and term infants needing oxygen therapy

Setting: NICU
Intervention: SET technology pulse oximetry
Comparison: standard pulse oximetry
effects*(95% CI) Certainty of
Relative № of
Risk with Risk with SET the
Outcomes effect participants Comments
standard technology pulse evidence
(95% CI) (studies)
pulse oximetry (GRADE)
oximetry
The
mean
MD 0.65
time
Time taken lower 380
taken to
to display (1.91 (2 ⨁◯◯◯
display
the data in lower to observational Very lowa,b
the data
seconds 0.61 studies)
in
higher)-
seconds
was 0
614 per 1,000 445
OR 0.99
617 per (523 to 700) (2 ⨁⨁◯◯
True alarms (0.68 to
1,000 observational Low
1.45)
studies)
307 per 1,000 445

OR 0.95
False 318 per (230 to 398) (3 ⨁⨁◯◯
(0.64 to
alarms 1,000 observational Lowc
1.42)
studies)
87 per 1,000 1026
OR 0.01
Dropout 904 per (87 to 159) (3 ⨁⨁⨁⨁
(0.01 to
alarm 1,000 observational HIGH
0.02)
studies)
Both oximeters accurately
measure heart rate. There was
good level of agreement
between HR measured by ECG
Agreement or any of the pulse oximeters
44
between using Bland Altman analysis.
(1
HR ECG The mean difference (HR ECG – -
observational
and Pulse HR Masimo)(±2 SD) was 0.2
study)
oximeters (±9.4)bpm, n=8694 in Masimo
group and in Nellcor group ,
the mean difference (HR ECG –
HR Nellcor) (±2 SD) was -0.8
(±10.9)bpm, n=9422.
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison
group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; MD: Mean difference; OR: Odds ratio
Explanations
a. Jeyapal et al show that The SET pulse oximeter picked up first saturation values faster than the RCAL technology
pulse oximeters. Pinnamaneni et al do not demonstrate any difference in total time for display between Masimo
group and Nellcor group b. There is significant heterogeneity between the trials c. The study by Workie et al did not
show any difference between the incidence of false alarms between the Masimo and Phillips group. However, in
the study by Hay et al there was a significant difference in the incidence of false alarms between Masimo and
Nellcor group.

Balance of benefits and harms

Dropouts alarm rate was lower in SET group in all the 3 studies evaluating this parameter, while
false alarm rate was lower in SET group in one of the 3 studies, thus implying higher accuracy.
No difference in true alarm rate and time taken to display the data was noted.
Values and preferences

The Bedside care givers may prefer a machine with more accuracy since it will avoid
unnecessary interventions in the baby as well as reduce alarm fatigue in the nursery. However,
SET technology is available only in limited brands of pulse oximeters (Masimo) which may not
be widely available. The benefit of reduced dropout rate with the SET group pulse oximeters
may make them preferable in neonates with hemodynamic instability, movement artefacts,
transport as well as in the delivery room.
Cost
Pulse oximeters using SET technology are expensive as compared to standard pulse oximeter.
technology. Standard pulse oximeters usually cost about 50-60% of SET technology pulse
oximeters.
RECOMMENDATION
7. In neonates on respiratory support pulse oximeters with or without signal

extraction technology may be used for monitoring of oxygen saturation.
Strong recommendation, High certainty of evidence
Justification : Strong recommendation based on similar true and false alarm rates with either
SET or non-SET technology endowed pulse oximeters although the only advantage of SET
technology pulse oximeters is lower incidence of dropouts, which may be beneficial in some
situations such as a neonate with hemodynamic instability, movement artefacts, transport as
well as in the delivery room.
Practice Question 8: Among preterm neonates on any respiratory support, does “closed-loop
fractional oxygen concentration regulation” compared to “manual regulation of oxygen” to
achieve desired saturation targets affect mortality or severe morbidities?
Background
Immature and surfactant deficient lung of preterm infants at birth need supplemental oxygen
for prolonged periods of time. Due to their lung pathology, their blood oxygen saturation
(SpO2) fluctuates widely necessitating frequent adjustments to the provided fraction of
inspired oxygen (FiO2) by the nursing staff. This may still be associated with variable periods of
time spent outside the intended SpO2 target range. Both hypoxia and hyperoxia may affect
long term outcomes.

Search strategy
We searched the Cochrane Register of Controlled Trials (CENTRAL) in The Cochrane Library,
PubMed and Google scholar using MeSH OR key words using filter clinical trial and clinical
trials period from 2000 to 2021. Cochrane database did not show any metanalysis related to
above topic. On searching PubMed with MeSH words, 7250 results were identified. Those not
meeting inclusions criteria or falling into exclusion criteria or duplicates were removed.
There are fifteen studies of closed loop automated oxygen control relating to neonatal
practice.40-52 These studies have compared time spent within, above or below target range.
Thirteen studies were randomized crossover study and two were retrospective. Retrospective
studies were excluded from meta-analysis. One study compared two levels of saturation. Data
which were presented as median (IQR) were converted as mean (SD) for meta-analysis. Meta-
analysis was done using Cochrane Revman software. The target SpO2 varied between the
studies with 85% being the lowest and 96% the highest. Overall, the sample size was small.
Patients’ gestational age at enrolment was mostly <30 weeks. The study duration ranged from
1.5 to 48 h, while infants were receiving mechanical ventilation, mechanical ventilation or non-
invasive support and non-invasive support.
There is one retrospective observation cohort study by Salverda et al53 recently published in
European journal of Pediatric which has compared two period i.e., period before and after
implementation of closed loop regulation of oxygen. Outcome compared were mortality and
complications of prematurity, number of ventilation days, and length of stay in NICU.
Summary of evidence
Table 6 shows the GRADE profile summary of evidence on effect of closed loop vs manual
regulation of fractional oxygen to achieve target oxygen saturation in preterm infants.
Evidence shows that mean difference in time spent within target oxygen saturation range is
15.47% (CI 9.72- 21.22) more for closed loop oxygen control than manual control. Mean
difference in time spent below and above target range are 1.32% (CI 0.43-2.21) and 8% (CI
2.56-13.43) respectively lower for closed loop oxygen control as compared to manual control.
Automated FiO2 control significantly improves SpO2 targeting and reduces periods of
hyperoxia, severe hypoxia, and hypoxic events in preterm infants receiving positive pressure
respiratory support. One retrospective observation study has shown no difference in critical
outcomes as shown in summary of evidence grade profile. Apart one retrospective cohort
study, the impact on mortality and long-term outcomes due to this small difference favoring
closed loop control is yet to be studied. Even if saturation targeting is a reliable surrogate
marker, we have limited knowledge of specific “thresholds” for clinical effects. While
refinements in the controlling algorithm would be beneficial, further studies should look at
clinical relationships including ROP, CLD, neurodevelopment and death. Quality of evidence
is very low for critical and important outcomes. Intervention is simple, but requires technology
and has a cost to implement.

Table 6: Summary of evidence
Certainty assessment № of patients Effect
Certainty Importance
№ of automated/Closed manual Relative Absolute
Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations
studies loop adjustment of fio2 (95% CI) (95% CI)
Time spent within the targeted saturation range (assessed with: pulse oximetry)
14 randomised serious b very serious c serious d not serious strong association 325 325 - MD 15.47 % IMPORTANT
higher
⨁◯◯◯
trials a VERY LOW
(9.72 higher
to 21.22
higher)
time spent above the targeted saturation (hyperoxia) (assessed with: pulse oximetry)
11 randomised serious b very serious c serious d not serious strong association 283 283 - MD 8 % IMPORTANT
lower
⨁◯◯◯
trials a VERY LOW
(13.43 lower
to 2.56
lower)
Time spent below the target saturation (hypoxia) (assessed with: pulse oximeter)
10 randomised serious b very serious c serious d not serious strong association 246 246 - MD 1.32 % IMPORTANT
lower
⨁◯◯◯
trials a VERY LOW
(2.21 lower
to 0.43
lower)
ETROP 1 (assessed with: ROP SCREENING)
1 observational very serious e not serious not serious very serious e,f publication bias strongly 22/250 (8.8%) 16/250 (6.4%) OR 0.71 18 fewer per CRITICAL
suspected (0.36 to 1.38) 1,000
⨁◯◯◯
studies VERY LOW
all plausible residual (from 40
confounding would suggest fewer to 22
spurious effect, while no more)
effect was observed e
Mortality at 1 month corrected age
1 observational very serious e not serious not serious very serious e,f publication bias strongly 32/296 (10.8%) 30/294 (10.2%) OR 1.07 6 more per CRITICAL
suspected (0.63 to 1.81) 1,000
⨁◯◯◯
studies VERY LOW
confounding would reduce fewer to 69
the demonstrated effect e more)

NEC >stage 2A
suspected (0.62 to 1.93) 1,000
⨁◯◯◯
studies VERY LOW
CULTURE PROVEN SEPSIS
1 observational very serious e not serious not serious very serious e,f publication bias strongly 121/295 (41.0%) 96/293 (32.8%) OR 1.43 83 more per IMPORTANT
suspected (1.02 to 2.00) 1,000
⨁◯◯◯
studies VERY LOW
all plausible residual (from 4 more
confounding would reduce to 166 more)
the demonstrated effect e
IVH STGE 2 OR MORE
studies suspected (0.58 to 1.35) 1,000
⨁◯◯◯
all plausible residual (from 70 VERY LOW
PVL STAGE 2 OR MORE
⨁◯◯◯
all plausible residual (from 8 fewer VERY LOW
confounding would reduce to 54 more)
the demonstrated effect e
Days in NICU
1 observational very serious e not serious not serious very serious e,f publication bias strongly 295 293 - MD 3 day IMPORTANT
studies suspected higher
⨁◯◯◯
all plausible residual (1.269 lower VERY LOW
confounding would reduce to 7.269
the demonstrated effect e higher)
SEVERE BPD
⨁◯◯◯

Moderate BPD
⨁◯◯◯
the demonstrated effect e fewer)
MILD BPD
1 observational very serious e not serious not serious very serious e,f publication bias strongly 38/258 (14.7%) 45/257 (17.5%) OR 0.81 28 fewer per IMPORTANT
⨁◯◯◯
ETROP STAGE 2
1 observational very serious e not serious not serious very serious e,f publication bias strongly 3/250 (1.2%) 9/250 (3.6%) OR 0.33 24 fewer per IMPORTANT
⨁◯◯◯
RECEIVED LASER COAGULATION
⨁◯◯◯
INVASIVE VENTILATION DAYS
1 observational very serious e not serious not serious very serious e,f publication bias strongly 295 293 - MD 1.7 days IMPORTANT
studies suspected lower
⨁◯◯◯
all plausible residual (3.195 lower VERY LOW
confounding would reduce to 0.205
the demonstrated effect e lower)
Explanations
a. includes both randomized and quasi randomized study (cross over studies)
b. sequence generation and /or allocation concealment not mentioned in most studies. Studies were not blinded
c. increased statistical heterogeneity observed across the studies
d. outcome studied are surrogate of BPD, mortality, and neurodevelopment outcome
e. retrospective study f. single study

Balance of benefits and harms: There is very-low certainty evidence that automated FiO2
control significantly improves SpO2 targeting and reduces periods of hyperoxia, severe
hypoxia, and hypoxic events in preterm infants receiving positive pressure respiratory support.
Although time spent at targeted saturation was better with closed loop and is likely to have
impact on incidence of ROP, NEC, BPD, PVL, the evidence does not show that it translates into
clinical benefits. Although evidence shown better control of targeting oxygen saturation with
closed loop there is still inadequate data from well conducted large studies for its effects on
mortality and morbidities. On the other hand, frequent manual adjustments of FiO2 to maintain
SpO2 within the target range is time consuming and challenging.
Values and preferences: The policy makers, families and physicians are likely to give high
preference to decrease duration of hypoxia or hyperoxia with automated FiO2 control. The
limitation is that it requires advanced ventilator availability which has the technology to
provide closed loop regulations of target oxygen saturation.
Costs: To accept the closed loop regulation of fractional oxygen to maintain desired oxygen
saturation range will require advanced ventilators which in turn will increase financial burden
to parent, policy maker and health care provider.
RECOMMENDATION
8. The guideline panel does not recommend for or against the use of closed-loop
oxygen therapy in neonates on respiratory support.
Weak recommendation, Very low certainty of evidence
Justification : Weak recommendation in view of very low certainty evidence showing more
time spent in saturation targets and very low certainty of evidence of no benefit or harm in
critical or important outcomes with use of closed-loop oxygen therapy.

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Oxygen Therapy in Neonates NNFI CPG Dec2021

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Clinical Practice

Guideline Writing Group (Alphabetical)

Editorial Board (Alphabetical)

© NNF India Online Version www.nnfi.org/cpg December 2021

A summary of the key recommendations is listed next in the table.

NNF India Evidence-based Clinical Practice Guidelines December 2021

SUMMARY OF RECOMMENDATIONS FOR OXYGEN THERAPY IN NEONATES

S. No. Recommendations Strength of Certainty of evidence

2. All neonates born at >34 weeks of Weak Not graded

3. All neonates with evolving / established Strong High

4. In neonates born at >34 weeks of Strong Moderate

5. In neonates being administered oxygen Weak Not graded

NNF India Evidence-based Clinical Practice Guidelines December 2021

6. In neonates on any respiratory support, Strong Not graded

7. In neonates on respiratory support pulse Strong High

8. The guideline panel does not Weak Very low

NNF India Evidence-based Clinical Practice Guidelines December 2021

Administration of oxygen to neonates improves survival in situations where lung immaturity,

SCOPE OF THE GUIDELINES AND TARGET AUDIENCE

NNF India Evidence-based Clinical Practice Guidelines December 2021

Panel 1 : Prioritized Clinical Practice Questions

Questions on oxygen saturation targeting

Modes of oxygen delivery

Techniques to improve compliance to oxygen saturation targeting

NNF India Evidence-based Clinical Practice Guidelines December 2021

Panel 2: Outcomes considered for this review

Relevance Outcomes Definition

Duration of oxygen Duration of oxygen therapy in days

NNF India Evidence-based Clinical Practice Guidelines December 2021

Data abstraction and summary tables of individual studies

Pooled treatment effect for developing recommendations were considered, wherever

Grading the quality of evidence

The following briefly describes how these criteria were used:

NNF India Evidence-based Clinical Practice Guidelines December 2021

NNF India Evidence-based Clinical Practice Guidelines December 2021

QUESTIONS, EVIDENCE SUMMARIES AND RECOMMENDATIONS

Characteristics of included studies

NNF India Evidence-based Clinical Practice Guidelines December 2021

NNF India Evidence-based Clinical Practice Guidelines December 2021

Table 1a: Summary of studies included in NeOProM Meta-analysis

NNF India Evidence-based Clinical Practice Guidelines December 2021

and 845 ± 197 difference adjusted 4. Even though the

NNF India Evidence-based Clinical Practice Guidelines December 2021

Table 1b: Summary of evidence table

Severe 90 per 1,000 112 per 1,000 RR 1.24 4929 ⨁⨁⨁⨁

Explanations: a. Treated with surgery or leading to death during initial hospitalization

NNF India Evidence-based Clinical Practice Guidelines December 2021

Costs: There is no difference in the cost of implementing a policy of higher as compared to

1. All preterm neonates born at ≤ 34 weeks of gestational age and requiring

Justification: Strong recommendation, based on evidence of high certainty demonstrating

NNF India Evidence-based Clinical Practice Guidelines December 2021

NNF India Evidence-based Clinical Practice Guidelines December 2021

Balance of benefits and harms

Weak recommendation, Not graded

Characteristics of included studies

NNF India Evidence-based Clinical Practice Guidelines December 2021

Sr. Study name Study Study Intervention Control Outcome Conclusions

NNF India Evidence-based Clinical Practice Guidelines December 2021

Table 2b: Summary of evidence table

Patient or population: Preterm infants with evolving or established BPD

Requirement of 61 per RR 0.54

NNF India Evidence-based Clinical Practice Guidelines December 2021

Table 2b: Summary of evidence table

Patient or population: Preterm infants with evolving or established BPD