J. Paediatr.

Child Health (2004) 40, 504505

Editorial Comment
Oxygen therapy and monitoring in newborn infants
MK Lal and S Sinha
University of Durham and The James Cook University Hospital, Middlesbrough, United Kingdom

Although ubiquitous and life saving, oxygen also has harmful

biochemical and physiological effects. Newborn infants are
particularly vulnerable to oxygen toxicity as they are often
exposed to high oxidative stress and have poor antioxidant
protection.1 In this situation, less exposure to oxygen would be
a simple and logical strategy that should reduce oxidative stress
and tissue injury. But we are faced with a dilemma because the
optimal range of oxygenation to balance for the four competing
risks in the newborn population, i.e. mortality, retinopathy of
prematurity (ROP)-blindness, chronic lung disease (CLD) and
brain damage (which are interrelated and not mutually exclusive) remains to this day unknown. It is therefore not surprising
that current practices of oxygen therapy vary from one institution to another depending on institutional preference or individual clinicians choice.
In this issue of the Journal, Saletti et al. describe their units
policy on discharging infants with CLD on home oxygen,
targeting oxygen saturation of more than 94%.2 They report
four-fold increase in the number of such infants as compared to
a similar cohort 10 years ago (10% vs 2.5% among infants
under 33 weeks gestation). This is despite the incidence of
chronic lung disease remaining constant around 20% in their
institution. This is also well above the rate of infants discharged
home in supplemental oxygen as recorded in Australia and
New Zealand Neonatal Network data for 2001, which was 6.8%
for infants < 34 weeks gestation. This unexpected increase in
numbers of babies receiving supplemental oxygen in this study
is more likely to be institution specific rather than a reflection
of a general trend and should be seen in the context of this
study only. The authors argue that oxygen therapy helps to
discharge such babies earlier is also not warranted from their
data as many other units, these days, will discharge such babies
earlier than an average of 40 weeks as noted in this study.
Similarly their assertion that oxygen therapy is safe in this
population may be contentious as data from recent studies point
to the contrary.
See related article, p 519.
Use of supplemental oxygen in infants with CLD is intuitively appealing and this is to do with concerns regarding
alveolar hypoxia, which may increase pulmonary vascular
resistance as well as airway resistance, limit somatic growth,
and perhaps also increase the risks of sudden death in infants
with CLD.35 In a cardiac catheterization study of infants with
CLD, supplemental oxygen was noted to improve hypoxic
vasoconstriction, resulting in decreased pulmonary vascular
resistance, but there are no longitudinal data on such infants.6

Groothuis and Rosenberg4 have also reported that supplemental

oxygen therapy at home leads to growth patterns comparable to
that of full-term infants, and, discontinuation of supplemental
oxygen in such babies may lead to deceleration of weight gain
pattern, which subsequently reverts to normal on resumption of
supplemental oxygen.
These observations, however, are not borne out in two recent
randomized controlled trials that have looked at how to optimize oxygen management in preterm babies when they are
more than a month old. The Supplemental Therapeutic Oxygen
for Pre-threshold Retinopathy (STOP-ROP) Trial7 published in
2000, used pulse oximetry to target lower (8994%) or higher
(9699%) oxygen saturation in 649 premature infants with
pre-threshold ROP. Infants in the supplemental group had more
adverse respiratory events, including pneumonia and CLD,
requiring further oxygen and diuretic therapy. The Benefits of
Oxygen Saturation Targeting (BOOST) Study8 published in
2003, recruited 358 infants born before 30 weeks gestation,
who were still in oxygen at 32 weeks postmenstrual age. Half
were given a masked oximeter that aimed to maintain a
saturation of 9194%, and the rest a saturation of 9598%. The
aim of this study was to see whether a higher saturation
improved growth and development at 12 months corrected age.
It did not and instead increased the time spent in oxygen and
the use of health care resources.
A number of non-randomized studies, including those of
Tin,9 Chow10 and McColm11 have also reported that targeting
lower oxygen saturations from birth may not only be associated
with reduced incidence of ROP in preterm infants but also be
advantageous in shortening the duration of assisted ventilation
and oxygen dependency, without adversely affecting death or
neurological abnormalities.
It is true that there is still considerable uncertainty regarding
what constitutes normal blood oxygen levels for infants, both
during the early neonatal period and later infancy. The temptation to leave preterm infants, in particular those with CLD,
on prolonged supplemental oxygen therapy may be based on
concerns as highlighted above, but we do not know whether
these associations are causal. It is also not known whether
oxygen-related interventions designed to, for example, reduce
desaturations, decrease pO2 variability, or improve sleep, actually make any significant difference to long-term outcomes that
are meaningful to children and their families.
Where do we go from here? Perhaps it is the time to admit
that we still do not know how to optimize the delivery of
supplemental oxygen particularly to the very preterm infants,
and agree to use the tool best suited to addressing this uncertainty such as a large randomized controlled trial with correct

Correspondence: Professor Sunil Sinha, Professor of Paediatrics and Neonatal Medicine, University of Durham and, The James Cook University
Hospital, Middlesbrough, UK. Email: Sunil.sinha@stees.nhs.uk
Accepted for publication 14 June 2004.

Oxygen therapy in newborn infants

hypothesis.12 Purists will argue that the findings of STOP-ROP

and BOOST trial relating to pulmonary outcomes were incidental data and that of Win Tin was only an observational study.
Nonetheless, their findings are provocative and provide useful
information for further clinical and epidemiological research. It
is encouraging to know that a number of important trials are
already being planned to address this issue but what do we do
until then? Should we continue to use oxygen therapy in the
historical manner simply because we were taught that oxygen
is good, with the implication that more must be better or
should we step back and recognize that supplemental oxygen,
with its potentially significant toxic effects, is a treatment that
should be used and monitored carefully?
This is further complicated by the lack of any reliable means
to measure oxygen tension in the blood, which is central to the
whole argument of benefits and risks. Despite the availability
of a number of tools including intermittent arterial blood gases
estimation, continuous arterial blood gases monitoring and
continuous non-invasive transcutaneous oxygen monitoring,
oxygen saturation measurement remains the most popular
choice. Pulse oximetry has gained widespread acceptance in
neonatal units because this is easy to use, does not require
calibration and gives almost immediate information regarding
changes in arterial oxygen saturation. There is little evidence,
however, of its effectiveness on clinically important outcomes.
The use of pulse oximeters also has technical and physiological
limitations. For instance, oximeters that display functional
oxygen saturation show a somewhat higher saturation
(1.53.0%) than those recording so-called fractional saturations
but more importantly, saturations more than 95% do not
correlate with oxygen tension in the blood which could be in
the hyperoxia range. It has also been hypothesized that it is the
variability of oxygen level11 rather than a threshold upper level,
which determines the toxic effects of oxygen, and hence it is
desirable that these monitors employ improved techniques such
as Signal Extraction Technology (SET),13 which seem to
significantly reduce false positive alarm rates.
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