Hypoxia Challenge Testing in

Neonates for Fitness to Fly

Susanne Vetter-Laracy, PhD, MD,a Borja Osona, MD,b Jose Antonio PeaZarza, MD,b Jose Antonio Gil, MD,b Joan Figuerola, PhD, MDb

BACKGROUND: Preflight hypoxia challenge testing (HCT) in a body plethysmograph has

abstract

previously been done only on infants >3 months of corrected gestational age (CGA). This
study aims to determine the earliest fit-to-fly age by testing neonates <1 week old.
METHODS: A prospective observational study was carried out on 3 groups of infants: healthy

term infants 7 days old, preterm infants (34 weeks CGA) 2 to 3 days before discharge,
and preterm infants with bronchopulmonary dysplasia (BPD). HCT was conducted using a
body plethysmograph with a 15% fraction of inspired oxygen. The oxygen saturation (SpO2)
test fail point was <85%.
RESULTS: Twenty-four term (mean CGA 40 weeks), 62 preterm (37 weeks), and 23 preterm
with BPD (39.5 weeks) infants were tested. One term infant (4.2%) and 12 preterm infants
without BPD (19.4%) failed. Sixteen (69.3%) preterm infants with BPD failed (P < .001),
with a median drop in SpO2 of 16%. At 39 weeks CGA, neither preterm infants without BPD
nor term infants had an SpO2 <85%. However, 7 of 12 term infants with BPD failed the HCT.
CONCLUSIONS: Term and preterm infants without BPD born at >39 weeks CGA do not appear to

be likely to desaturate during a preflight HCT and so can be deemed fit to fly according to
current British Thoracic Society Guidelines.

Divisions of aNeonatology and bPaediatric Respiratory Medicine, Department of Paediatrics, University Hospital
Son Espases, Palma de Mallorca, Spain

Drs Vetter-Laracy and Osona conceptualized and designed the study, carried out the initial
analysis and interpretation of data collection, and drafted the initial manuscript; Drs Pea-Zarza,
Gil, and Figuerola made substantial contributions to conception and design and reviewed and
revised the manuscript; and all authors coordinated and supervised data collection, approved
the nal manuscript as submitted, and agree to be accountable for all aspects of the work
in ensuring that questions related to the accuracy or integrity of any part of the work are
appropriately investigated and resolved.
DOI: 10.1542/peds.2015-2915
Accepted for publication Dec 2, 2015

WHATS KNOWN ON THIS SUBJECT: Preterm

infants 3 months of corrected gestational age
and without bronchopulmonary dysplasia are at no
greater risk of hypoxia compared with term infants
during a preight hypoxic challenge test in a body
plethysmograph thus can be considered t to y.
WHAT THIS STUDY ADDS: Preterm and term infants
without pulmonary problems from a corrected
gestational age of >39 weeks are not at risk for
hypoxia during a preight hypoxic challenge test in a
body plethysmograph.

Address correspondence to Susanne Vetter-Laracy, Department of Paediatrics, Division of

Neonatology, University Hospital Son Espases, Carretera Valldemossa 79, 07120 Palma de
Mallorca/Spain. E-mail: vettersusan@yahoo.com
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright 2016 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have no nancial relationships relevant
to this article to disclose.
FUNDING: No external funding.

To cite: Vetter-Laracy S, Osona B, Pea-Zarza JA, et al.

Hypoxia Challenge Testing in Neonates for Fitness to Fly.
Pediatrics. 2016;137(3):e20152915

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conicts of
interest to disclose.

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PEDIATRICS Volume 137, number 3, March 2016:e20152915

ARTICLE

Commercial planes fly at 9000

to 13000 m, requiring cabin
pressurization to 1530 to 2440 m.
At this altitude, the reduced pO2 is
equivalent to breathing 15% oxygen
(fraction of inspired oxygen [FIO2]
0.15) at sea level. It is already well
known that pulse oxygen saturation
(SpO2) declines significantly in
healthy children and adults (4%,
down to 94.4%) during commercial
airline travel, but this is not
considered pathologic.1,2 Newborns
are particularly susceptible to
hypoxemic episodes in a hypoxic
environment because of factors
such as an increased tendency for
ventilation-perfusion mismatch and
a left shift of the oxygen dissociation
curve due to fetal hemoglobin in
the first months of life.3 Premature
infants have more apneic pauses
and periodic breathing when they
reach term than term infants, and
apneic pauses may be triggered by
chronic hypoxemia.46 Thus, studies
testing term infants and premature
infants during the first months of life
for fitness to fly have been ruled out
by most other researchers despite
the fact that the number of families
wanting to take their newborns on
flights shortly after delivery has
increased.711
The British Thoracic Society
(BTS) has published guidelines for
infants stating that term newborns
(>37 weeks) should wait 1 week
after birth term before traveling,
premature infants who have not
reached term should have in-flight
oxygen of 1 to 2 L/min (grade C
evidence), and premature infants
<1 year old with neonatal chronic
respiratory problems should undergo
hypoxia challenge testing (HCT).12,13
Son Espases neonatal unit is located
on Mallorca, the largest of the
Balearic Islands and a major tourism
hub in the Mediterranean Sea. An
average of 29 premature births to
nonresident mothers take place
annually. Approximately 9 premature
infants are born on the surrounding

islands each year and are transferred

to our center for follow-up. It is
therefore necessary to assess the
safety of flying for neonates of
mothers not residing on Mallorca.

BPD. BPD was evaluated at 36 weeks

CGA and was defined as the need for
supplemental oxygen for 28 days,
per National Institute of Child Health
and Human Development criteria.12

No other fitness-to-fly testing

has been conducted in a body
plethysmograph on healthy term
infants in the first week of life and
premature infants at term age.
The objective of this study was to
determine the earliest fit-to-fly age
of preterm and term infants. This
was done by testing preterm infants
at term age, including those with
bronchopulmonary dysplasia (BPD),
and comparing the results with a
control group of healthy infants that
were 7 days old.

Fitness-to-fly testing was performed

according to the testing protocol in
the Pediatric Pulmonary Function
Testing Laboratory, Pediatric
Respiratory Unit, University Hospital
of Son Espases, from September 2010
to May 2013.

METHODS
This was a prospective observational
clinical study. Term infants (37
weeks gestational age [GA]) and
2 days and 7 days old were
recruited from the postnatal ward
of the University Hospital Son
Espases, Palma de Mallorca. Preterm
infants (<37 weeks GA and 34
weeks of corrected gestational
age [CGA]) were selected shortly
before discharge from the neonatal
unit. All parents of included infants
were planning a flight shortly after
discharge. Written informed consent
was given by all parents. Ethics
approval was granted by the Ethics
Committee of Clinical Investigation of
the Balearic Islands (IB 1231/09).
The condition for all included
infants was a baseline SpO2 of >94%.
Exclusion criteria were respiratory
infection 1 week before testing,
current oxygen requirement, and
cardiac, respiratory (other than BPD),
or metabolic disease. Birth history
and all clinical data were obtained
from patient reports.
The infants were divided in 3 groups:
Group 1, term infants; Group 2,
premature infants without BPD; and
Group 3, premature infants with
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The HCT was performed with the

infant on the caregivers lap sitting
inside a sealed body plethysmograph
(MasterScreen Body, Erich Jaeger).
To test all infants in the same
conditions, the infants needed to
remain awake and in a half-seated
position without flexing the neck and
without being fed.
SpO2 and pulse rate of the newborns
were measured continuously with a
Masimo SET Radical-7 Electron pulse
oximeter attached to the infants
hand or foot. Readings were taken
after a stable plateau was reached,
and baseline SpO2 and pulse rate in
room air were recorded. Nitrogen
was added into the chamber with
a flow of 50 L/min, gradually
reducing the FIO2 to a concentration
of 15% (O2 concentration was
measured by MiniOx3000, Medical
Products). FIO2, SpO2, and pulse
rate were continuously observed for
20 minutes, at which point timing
and any changes were also noted.
If SpO2 dropped to <85%, oxygen
was administered immediately in
a nasal cannula until the baseline
SpO2 was reached. The minimum
amount of supplemental oxygen
given was recorded. An SpO2 of <85%
was counted as a test fail, and the
newborn was deemed not fit to fly.
If the newborns failed the HCT it was
recommended supplemental oxygen
be given on board flights ,as outlined
in BTS guidelines.13,14 Parents were
then requested to repeat the test
every 2 months until obtaining fit-tofly status. For families living on the

VETTER-LARACY et al

TABLE 1 Demographic and Clinical Data of the Tested Groups

Characteristic

Group 1, Term

Group 2, Preterm Without

BPD

Group 3, Preterm With

BPD

n
Mean GA, wksa
Male, n (%)
Mean birth weight, kga
Mean age, da
Mean corrected age,
wksa
Days of oxygen therapyb
Days of mechanical
ventilationb
Days of CPAPb
Days without oxygen
therapyb

24
39.6 (39.140)
12 (50)
3.3 (33.4)
3 (33.8)
40 (39.640.5)

62
32.5 (31.933)
36 (58)
1.8 (1.71.9)
27 (14.546.5)
37 (36.537.6)

23
28.2 (2729.5)
10 (43)
0.9 (0.81)
78 (64.4102.3)
39.5 (38.140.9)

1 (04)
2 (15)

47 (4473)
8 (111)

0 (02)
25 (12.342)

12 (226)
18 (1336)

Data are a mean (95% CI) or b median (interquartile range).

preterm with BPD. All term infants

were healthy and had uneventful
deliveries. Complications suffered by
preterm infants during their hospital
stay were resolved by the time of
testing. Demographic and clinical
data for all newborns are listed in
Table 1.

Test Results, Predictors of Test

Failure, and Comparison Between
Groups
One 5-day-old healthy term infant
(38 weeks, 1 day GA) failed the test
(1 of 24, 4.2%). SpO2 dropped to 82%

TABLE 2 Test Results and Comparison of Groups

Characteristic

n
Baseline SpO2, %
Change in SpO2
Time to reach lowest test SpO2,
min
Lowest test SpO2, %
Time until failing test, min
Baseline pulse rate, beats per
min
Highest test pulse rate, beats
per min
Pulse rate during desaturation,
beats per min
Test failure SpO2 <85%, n (%)
SpO2 <90% during test, n (%)

Group 1, Term

Group 2, Preterm Without

BPD

Group 3, Preterm With BPD

24
99 (97100)
9 (811)
10 (1015)

62
99 (98100)
8 (612)
15 (1018)

89 (8890)
20a
138 (121153)

P
Group 1 vs 2

Group 1 vs 3

Group 2 vs 3

23
99 (96.599.5)
16 (1019)
8 (512)

NS
NS
NS

NS
.001
NS

.015
<.001
.003

91 (8794)
10 (812)
159 (147170)

81 (8088)
8 (59)
158 (13870)

NS

<.001

.001

NS

<.001
NS
NS

152 (141162)

169 (160179)

163 (157177)

NS

NS

.015

127

148 (143163)

158 (144177)

NS

1 (4.2)
12 (50)

12 (19.4)
21 (33.9)

16 (69.6)
19 (82.6)

NS
NS

<.001
NS

<.001
<.001

Data are median (interquartile range). NS, not signicant.

a Only 1 term infant failed the test.

surrounding islands, a ferry

trip home was recommended in all
cases.
After a power calculation, we
simulated the recruitment of 54
patients in the study with 18 patients
in each of the 3 groups. Descriptive
analysis was performed calculating
median and quartiles, or mean and
95% confidence interval (CI) if
variables were normally distributed.
To contrast the hypothesis, the test of
MannWhitney and KruskalWallis,
or Student t test and analysis of
variance, were used. To describe
qualitative variables, proportions
and 95% CI were calculated. An
exploratory analysis using binary
logistic regression was used to

PEDIATRICS Volume 137, number 3, March 2016

calculate the adjusted effect over

desaturation as a dependent variable
of several independent variables.
Odds ratios (ORs) are presented with
95% CIs and used for variables with
significant association. All statistical
tests were 2-tailed, and for differences
between groups, a Bonferronicorrected P value <.016 was
considered significant. IBM Statistics
SPSS 20.0 software was used.

RESULTS
Demographics
From September 2009 to May 2013,
109 infants were tested: 24 term,
62 preterm without BPD, and 23
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and the infant needed 0.5 L/min of

oxygen to recover. Pulmonary or
cardiac diseases were excluded by
image studies in this infant. Twelve
of the 62 preterm infants (19.4%)
without BPD and 16 of 23 preterm
(69.3%) with BPD had SpO2 <85%
during the test. The test results are
listed in Table 2.
After a CGA of 39 weeks, none
of the preterm infants without
BPD and none of the term infants
desaturated <85%, but 7 of 12
infants >39 weeks with BPD failed
the test (Figs 1 and 2). BPD was
a strong predictor of failing the
HCT, with an OR of 17.2 (95% CI
4.860.9; P < .001).

Term and preterm infants without

BPD in our study had an important
drop in SpO2 during the preflight
test (9% and 8%, respectively).
Interestingly, we found that all
neonates >39 weeks CGA and those
without BPD passed the test.
Similar results to these were found in
previous studies conducted on older
infants, as in the studies of Bossley
et al,7 who tested term and preterm
infants of 3 and 6 months CGA, and
Martin et al,15 who tested healthy
term infants (13221 weeks old)
and found that only 1 of 24 healthy
children desaturated.
Our data are not in accordance with
the results of Udomittipong et al,16
who found that a high proportion
(38 of 47) of preterm infants with a
median corrected age of 1.4 months
are at a high risk of in-flight hypoxia.

FIGURE 1
Individual test results of premature and term infants. SpO2 of infants tested after 39 weeks CGA (16
term and 12 preterm) did not fall below 85%.

As mentioned above, a significant

difference was observed between
preterm infants with BPD and
neonates without BPD. There was
a significant drop in SpO2 (P = .001)
during the test comparing infants
who were term or preterm without
BPD (median change 9 and 8,
respectively) versus preterm with
BPD (median change 16).
Minimum SpO2 during the test was
significantly lower in infants with
BPD (median 81%, interquartile
range 80%88%, P < .001) compared
with the other 2 groups. The BPD
infants reached the minimum SpO2
earlier (8 minutes, P = .003) than
preterm infants without BPD (15
min).
The 16 BPD patients who failed the
test needed 0.5 to 1 L/min of oxygen
to recover, and the 12 preterm
infants without BPD needed 0.5 to
2 L/min (only 2 children needed 2
L/min). Twelve of the infants had
mild BPD, 9 moderate BPD, and 2

severe BPD.12 Unexpectedly, time

without supplementary O2 was not a
significant factor in passing the test
(Table 1).
The term infant who failed the HCT
did not repeat the test 2 months later
as advised. Only 2 of the preterm
infants without BPD repeated the
test, at 5 and 6 months CGA; both
passed the second time.
Seven of 16 preterm infants with
BPD repeated the test. Of these, 3
at 2 months and 2 at 6 months CGA
passed. One child with BPD was
retested at 6 months CGA and failed
again. Another preterm infant with
BPD born at 23 weeks GA was first
tested at 42 weeks CGA and was
retested at 7 and 17 months CGA, but
failed all HCTs.

DISCUSSION
SpO2 declines 4% in healthy
children and adults while in flight.1,2
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The discrepancy in results with

Udomittipong et al may be due to the
different test methods used. We used
a whole-body plethysmograph during
the test, which is recommended in
the BTS guidelines. Udomittingpong
et al16 and other studies on infants
of a similar age used high-flow (15
L/min) 14% oxygen in nitrogen
via a non-rebreathing facemask
incorporating a 1-valve assembly.
This method may not be reliable
when used with infants, as has been
suggested by other authors.15
Neonates >39 weeks CGA without
BPD who reach term age have a test
behavior similar to that of older
infants, so the necessity for an HCT
could be eliminated for this group.
In-flight oxygen may not be necessary
either.
BPD was highly associated with test
failure, with an OR of 17.2. Infants
with BPD also suffered a median
drop in SpO2 of 16% (P = .001), and
69.6% of BPD infants failed the HCT
and thus were deemed unfit to fly. In
2004, Buchdahl et al17 performed a
retrospective review of test results in
infants with BPD and discovered that
8 of 20 patients desaturated during

VETTER-LARACY et al

can influence the obstruction of the

upper airway), and feeding may have
an impact on oxygen saturation.57
Therefore, we decided to standardize
conditions as much as possible and
tried to avoid introducing variables.
The BTS guidelines do not establish
recommendations in reference to
the mentioned conditions even
though they can have an important
impact on the results. Further studies
are needed that analyze similar
populations for the significance of
sleep or change of body position.

FIGURE 2
Individual test results of premature infants with BPD. Seven of 12 infants >39 weeks CGA failed the
HCT.

the HCT, whereas Udomittipong

et al in 200616 found that 23 of 32
preterm infants with BPD failed the
HCT.
The improvement of failure rates
in our study observed in term and
preterm infants without BPD when
they reached >39 weeks CGA was not
evident among the infants with BPD
(Fig 2). It has to be mentioned that
infants with BPD had a considerably
lower GA (28.2 vs 32.5 weeks); thus
extreme prematurity might have an
influence on the test result.
The strengths of this study include
the relatively large number of
patients tested and their young
age; infants so young have not been
tested before. Also, the infants were
tested in a body plethysmograph, the
recommended method in the BTS
guidelines. Limitations include the
time of testing and the conditions of
testing (awake without feeding), and

PEDIATRICS Volume 137, number 3, March 2016

that accuracy of HCT results was not

confirmed by comparison with actual
inflight SpO2 in the tested infants.
It is possible that the testing time of
20 minutes may not be long enough
and thus not generate sufficient
data to predict safety limits for longdistance flights, as SpO2 usually
decreases in proportion to the
duration of hypoxemia.1,9 Most of our
test patients who failed desaturated
in 8 to 10 minutes; however, the only
term child who failed did not drop
to <85% until the end of the testing
period.
The HCT was carried out with the
infant awake without feeding and
without decubitus position. The
authors are aware that all those
factors and others (duration of the
test, humidity, infections of the upper
airways, noise, etc) vary greatly
during flight. It is true that active
sleep, changes of position (which
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Many studies have proved the HCT to

be equivalent to in-flight conditions
and hypobaric chamber results
in adults and children.1821 Two
studies were recently conducted by
an Australian group to assess HCT
accuracy by using a non-rebreathing
mask on infants. They published data
of 46 preterm (35.8 weeks) and 24
term infants >2 weeks old, finding
false-positive and false-negative
HCT results compared with in-flight
SpO2.10,22
The studies that concluded that the
HCT is unreliable in infants both
used facemasks to do the testing,
and this is thought to be a flaw,
as false-positive results due to
immediate exposure to FIO2 of 14%
or crying or false-negative results
due to insufficient sealing of the mask
and air room entrainment can be
responsible for the discrepancy of
test and in-flight results.15,22,23
In the first study, done on preterm
infants, the range of time between
HCT and flight was 1 to 15 days.10
A delay of 2 weeks might change
the condition of a premature infant
considerably and could explain the
differences between the results. In
the study done on term infants, the
inflight SpO2 nadir was 5% lower
than the HCT nadir. Flight duration
may also play a role, as 3 children
had SpO2 both below and above
85% on different flights. Sitting in
a sealed chamber in 15% oxygen is
presently the best method available
for simulation of in-flight conditions,

but further studies are needed to

prove the accuracy of the HCT in a
plethysmograph in term and preterm
infants.
In another recent study from
Australia, SpO2 of infants <6 months
old was monitored during aircraft
transport, and no difference in the
incidence of desaturation was found
between children <6 and >6 weeks
old.24 This could support our data
that young infants are able to fly. The
cutoff limit in the study was 94%,
which explains the high incidence
of desaturations in all age groups
(one-third). In 2011, the cutoff limit
of the HCT was changed in the BTS
guidelines from SpO2 90% to 85%.14
If it is set to 90%, the probability to
fail the test increases in all groups,
especially in healthy infants (Table
2).15,25 An explanation for the high
failure rate of term infants in our
study if SpO2 is set to <90% in
comparison with preterm infants
could be the younger chronological
age of term infants and a shorter
adaptation period to extrauterine
life (eg, higher amount of fetal
hemoglobin in term infants). If a
temporal SpO2 of 85% to 90% has
any negative impact on infants, it is
still not clear.8
The HCT via body plethysmograph
represents a reasonable
approximation of the physiologic
changes infants undergo in a hypoxic
environment and is useful for
advising a family about the risk of
commercial air travel and the need
for oxygen during a flight.

CONCLUSIONS
This study shows that over a period
of 20 minutes in a controlled
environment with an FIO2 of 15%,
SpO2 levels remain within safe limits
for healthy term infants >39 weeks
CGA and also for preterm infants
>39 weeks CGA without BPD. The
majority of infants with BPD do not
maintain safe levels of SpO2 even in
a simulated in-flight environment,

and therefore testing at this early

age might not be useful. It is
recommended to delay the test until
the infant is 1 year old.

ACKNOWLEDGMENTS
We thank the nurses of the Paediatric
Functional Testing Laboratory who
gave careful technical effort to the
study. Thanks also to the medical
staff of the maternity ward and to
the families of the participating
infants. Particular thanks to Gerard
Laracy for his extensive effort and
commitment to the editing and
proofreading of this manuscript.

ABBREVIATIONS
BPD:bronchopulmonary
dysplasia
BTS:British Thoracic Society
CGA:corrected gestational age
CI:confidence interval
FIO2:fraction of inspired oxygen
GA:gestational age
HCT:hypoxia challenge testing
OR:odds ratio
SpO2:pulse oxygen saturation

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Hypoxia Challenge Testing in Neonates for Fitness to Fly

Susanne Vetter-Laracy, Borja Osona, Jose Antonio Pea-Zarza, Jose Antonio Gil and
Joan Figuerola
Pediatrics 2016;137;1; originally published online February 15, 2016;
DOI: 10.1542/peds.2015-2915
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned, published,
and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk
Grove Village, Illinois, 60007. Copyright 2016 by the American Academy of Pediatrics. All
rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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Hypoxia Challenge Testing in Neonates for Fitness to Fly

Susanne Vetter-Laracy, Borja Osona, Jose Antonio Pea-Zarza, Jose Antonio Gil and
Joan Figuerola
Pediatrics 2016;137;1; originally published online February 15, 2016;
DOI: 10.1542/peds.2015-2915

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
/content/137/3/1.37.full.html

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2016 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

Downloaded from by guest on March 14, 2016