Apnea, Transient Episodes of Bradycardia, and
Periodic Breathing in Preterm Infants
Joan E. Hodgman, MD; Felipe Gonzalez, MD; Toke Hoppenbrouwers, PhD; Luis A. Cabal, MD
\s=b\ The occurrence of central apnea of 15
seconds or longer, transient episodes of
bradycardia (TEB), and periodic breathing
were studied in 66 healthy premature in-
fants when at least 1 week old and be-
tween 32 and 36 weeks postconceptual
age. Eight-hour cardiorespiratory record-
ings were visually scanned for the pres-
ence of thesee patterns. Central apnea of
15 seconds or longer was seen in almost
half of the infants. The TEB were numer-
ous, and the majority were not associated
with central apnea; however, all but five of
the apneic episodes that lasted 15 sec-
onds or longer were accompanied by a
TEB. Infants spent as much as 40% of their
time in periodic breathing. The frequency
with which these patterns are seen in
healthy premature infants strongly sug-
gests that they are normal findings. Our
results do not support the opinion that
brief periods of apnea are abnormal when
accompanied by a TEB.
(AJDC. 1990;144:54-57)
^/"ith the advent of continuous cardio-
respiratory monitoring of the pre¬
mature infant, a variety of interesting
and sometimes seemingly ominous pat¬
terns have been identified in the respi¬
ratory and cardiac tracings. Most com¬
monly noted are apnea, transient
episodes of bradycardia (TEB), and pe¬
riodic breathing (PB).111 Before attrib¬
uting pathologic significance to these
patterns, their occurrence in the
healthy infant needs to be established.
Quantification of these patterns is still
incomplete. Many previous reports
have been based on small numbers of
infants who are at varying ages or have
included those who are symptomatic.
Few investigators have examined all of
these patterns simultaneously in the
same infants. The purpose of this study
was to define the incidence of central
apnea, TEB, and PB in a carefully se¬
lected large group of healthy premature
Accepted for publication March 9,1989.
From the University of Southern California
School of Medicine and Los Angeles County\p=m-\
University of Southern California Medical Center,
Los Angeles, Calif.
Reprint requests to LAC/USC Medical Center,
Women's Hospital, Room L-919, 1240 N Mission
Rd, Los Angeles, CA 90033 (Dr Hodgman).
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infants between 32 and 36 weeks post- ed. The duration of an apneic episode was
conceptional age in a nursery setting. measured from the end of the inspiration
before the pause to the beginning of the next
SUBJECTS AND METHODS inspiration. One deflection during a pause
was discounted (Fig 1). A TEB was defined
as a drop in heart rate below 90 beats per
Daily admissions to the intensive and in¬ minute. The duration of the TEB was mea¬
termediate care nurseries were reviewed to sured from the time the heart rate started to
identify potential candidates for the study. decrease until the maximum point of recov¬
Sixty-six consecutive healthy premature in¬ ery (Fig 1). Periodic breathing was defined
fants appropriate for gestational age were as a visual pattern of repetitive short central
selected for the study when they were at pauses separated by bursts of respirations
least 7 days old and 32 to 36 weeks of postcon- (Fig 2). To qualify, the pauses had to be
ceptional age. The more mature infants (>34 between 3 and 10 seconds in duration sepa¬
weeks' gestational age) were frequently dis¬ rated by respiratory pauses lasting 20 sec-
charged by 1 week and were therefore un¬
available for study. Gestational age was
determined by maternal history if the
Dubowitz score12 agreed within 2 weeks. If
there was a larger discrepancy, the gesta¬
tional age that was closest to the 50th percen-
tile for head circumference using the Denver
Intrauterine Growth Curve13 was assigned.
Infants with the following clinical or bio¬
chemical findings that might predispose to
apnea were excluded: a 5-minute Apgar
score below 7, supplemental oxygen for more
than 24 hours, assisted ventilation including
continuous positive airway pressure, intra-
cranial hemorrhage grades III or IV, sepsis
proved by culture, diagnosed medical condi¬
tions, anemia (hematocrit value <0.30 after
the first week), and biochemical abnormali¬
ties of glucose, sodium, or calcium. None of
the infants were receiving medications other
than the routine administration of vitamins,
and they were all fed by nipple or gavage at
the time of study.
Cardiorespiratory monitoring (using a
Corometrics Neonatal Monitor 512, Corome-
trics, Wallingford, Conn) was carried out
during an 8-hour period starting at approxi¬
mately 11 PM. This monitoring is part of the
routine care in our special care nurseries and
is included in the consent process for all hos¬
pital admissions. Respirations were record¬
ed by impedance pneumography, and the in¬
stantaneous heart rate was calculated from
the RR interval of the electrocardiograph.
The 8-hour tracings were visually scanned.
While obstructive apnea cannot be reliably Fig 1 .—Central apneic episode of longer than
identified from these tracings, central apneic 20 seconds, with one deflection on the lower
respiratory tracing associated with a transient
episodes can be readily recognized.14 Short episode of bradycardia of longer than 20 sec¬
central apnea of less than 15 seconds in dura¬ onds, with a peak drop to 90 beats per minute
tion was encountered so frequently in all of in the upper cardiac tracing. Numbers in the
the records that no attempt was made to upper segment refer to beats per minute.
count all the episodes. All central apnea of 15
Each large section equals 1 minute, while
seconds or longer was measured and count- each small section represents 10 seconds.
 onds or less, and the pattern had to persist
for at least 30 seconds.7 Regular breathing
correlates well with quiet sleep, but irregu¬
lar breathing occurs in both active sleep and
awake states in premature infants. Conse¬
quently, it is not possible to report our re¬
sults in relation to sleep state. When appro¬
priate, 2 analysis was used to ascertain
differences between variables.
RESULTS
The gestational ages and birth
weights of the patient population are
shown in Table 1. The infants were all
appropriate for gestational age, which
is reflected in the mean birth weights.
The median gestational age was 32
weeks, and the majority of infants were
210-
180-
120
-90-
-60-
-30-
between 32 and 33 weeks of gestation at categories in Fig 3. A sharp drop in the
birth. For evaluation of the results, in¬ incidence of longer apnea occurred in
fants were divided into three groups, infants 33 weeks old and older at birth.
those at the median gestational age of 32 There was a total of 94 individual ap¬
weeks, those younger, and those older. neic episodes of 15 seconds or longer.
The study design required that infants Twenty of the 94 episodes lasted 20 sec¬
born at shorter gestations be studied at onds or longer, and 5 of these were be¬
older postnatal ages to achieve compa¬ tween 30 and 40 seconds in duration.
rable postconceptual ages. Our nursery protocol dictates observa¬
tion of the infant at 20 seconds, skin
Apnea stimulation at 30 seconds (unless clinical
Approximately half of the infants signs of cyanosis or pallor are present
(53%) had no apneic episodes of 15 sec¬ earlier), and ventilation with a mask and
onds or longer. When examined by ges¬ bag if there is no response by 40 sec¬
tational age, 25%, 44%, and 76% of the onds. The 5 prolonged apneic episodes
infants less than, equal to, and greater reported herein responded to skin stim¬
than 32 weeks old, respectively, did not ulation, and none needed intervention
demonstrate apneic episodes of 15 sec¬ by mask and bag ventilation.
onds or longer (Fig 3). Twenty-five Lower 1-minute Apgar scores were
(38%) of the total number of infants had associated with more frequent long ap¬
one or more 15- to 19-second apnea, and neic episodes after the first week oflife.
in 10 infants (15%), the duration was 20 Although all of the infants' 5-minute Ap¬
seconds or longer. Four of these 10 in¬ gar scores were above 6 by study de¬
fants (6% of the total population) had sign, 6 (33%) of the 18 with a 1-minute
two or more episodes of apnea of this score of 6 or less had apnea of 20 seconds
duration. Four infants had apnea that or longer as compared with 4 (8%) of 48
lasted both 15 to 19 seconds and 20 sec¬ with 1-minute scores of 7 or above
onds or longer and are included in both (P<.05).
Table 1 .—Clinical Characteristics of Patient Population
Mean ± SD
Gestational No. of Birth Postnatal
Age, wk Infants Weight, g Age, d
28 3 1233±60 28±3
29 1 1480 21
30 2 1340±57 18±3
31 10 1591 ±192 16 + 8
32 25 1696±279 11+5
33 10 1724±227 10±4
34 14 1889±194 8±2
35 1 2050 7

Fig 2.—Periodic breathing with respiratory

bursts of 8 to 10 seconds separated by
10-second pauses in the lower segment. Nor¬
mal heart rate with normal variability at 137 to
152 beats per minute is shown in the upper
segment. Measurements are the same as
those in Fig 1.

Table 2.—TEB and Apnea Duration*

Duration of TEB, s
(No. [%])
Duration No -*-

of Apnea, s TEB 20 -20

None-==15 110 (68) 47 (55)
15-19 5
...
34 (21) 35 (41)
a20 0 17 (11) 3 (4)
Total 5 161 (100) 85 (100)
*TEB Indicates transient episodes of bradycar¬
dia.

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Fig 4.—Duration of periodic breathing (in minutes per 8-hour tracing) as a function of gestation¬
al age. Ordinate indicates the percentage of infants exhibiting periodic breathing of various
durations.
TEB
Decreases in heart rate to less than 90
beats per minute were a common occur¬
rence. Forty-five infants (68%) showed
TEB, with a range of 1 to 18 episodes
and a mean of 2.6 in the 8-hour tracing.
One third (85) of the total 246 TEB
lasted for 20 seconds or more, while two
thirds (161) were brief, lasting for less
than 20 seconds (Table 2). Sixty-eight
percent of these brief TEB occurred
without evidence of central apnea of 15
seconds or longer. When TEB of 20 sec¬
onds or longer were considered, 55%
were still not associated with central
apnea of 15 seconds or longer. While the
majority of TEB did not accompany a
long apneic episode, all but 5 of these
apneic episodes of 15 seconds or longer
were accompanied by a TEB.
PB
Eight infants had no PB during the
approximately 480 minutes of record¬
ing, 37 exhibited PB for 1 to 49 minutes
(up to 10%) ofthe recording time, 12 had
PB between 50 and 99 minutes (10% to
20%), while 9 infants breathed periodi¬
cally for more than 100 minutes (>20%)
(Fig 4). The mean number of minutes of
PB was 47.5, with a large SD of 45.2
minutes and a range of 2 to 195 minutes.
The mean percentage of total recording
time spent in periodic breathing was
9.92, and the median percentage for
those infants exhibiting periodic
breathing was 8.90. As can be seen in
Fig 4, there was a tendency for less
mature infants, those younger than 33
weeks of age, to spend more time
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breathing periodically. Of the 9 infants
who spent more than 20% of their time
in PB, none exhibited apnea between 15
and 19 seconds, and only 1 had apnea of
20 seconds or longer, suggesting that
PB does not predispose to apnea in
healthy premature infants. This is also
supported by the observation that only
one fifth of the 94 episodes of apnea 15
seconds or longer described above oc¬
curred during PB.
COMMENT
All of the patterns described herein
were common in healthy premature in¬
fants. Central apnea of 15 seconds or
longer was seen in almost half of the
infants. The TEB were numerous and
most were not associated with central
apnea. Infants spent as much as 40% of
the recording time in PB. There was
considerable variation among individual
infants in all the parameters. The inci¬
dence of apnea and PB decreased after
32 weeks of gestational age.
Comparison of our results with previ¬
ous reports is difficult due to variance in
both study populations and methods.
Investigators who studied premature
infants agree that episodes of apnea 20
seconds or longer are seen in healthy
infants, that the incidence of apneic epi¬
sodes decreases with both increasing
gestational and chronologic ages, and
that the variability among infants is
large.4*10 Our data support these conclu¬
sions. Daily et al4 reported an incidence
of 30% for apneic episodes of 20 seconds
or longer in all premature infants after
the first week. This figure is twice that
found in the present study but included
symptomatic as well as healthy infants.
While prolonged apnea occurred in 15%
of our infants, repetitive episodes of this
duration were seen in only 6%. Thus,
within this healthy group, 6% of the
infants would be classified as having
clinically significant apnea using our
current definition of repetitive pro¬
longed episodes. Of interest, a low
1-minute Apgar score was associated
with a significant increase in prolonged
apnea after the first week of life even
though the infants had no other clinical
findings.
The TEB were common, occurring in
45 (68%) ofthe 66 recordings. This heart
rate pattern was described in the
healthy infant as early as 196315 and can
be equated with the benign v-shaped or
type 1 dips of the fetal heart rate.16 Sev¬
eral previous studies of TEB in conjunc¬
tion with apnea as well as the present
report found this pattern to increase in
incidence with increasing duration of
the apnea and to decrease with increas¬
ing gestational and chronologic age.917"19
We found that the majority of TEB
occurred without central apnea. Smith
and Milner,20 using impedance pneumo-
graphy and observation, also reported
that many TEB were not associated
with central apnea but rather with
changes in respiratory pattern and so¬
matic movement. In both Smith and
Milner's study and ours, some of these
episodes may have represented ob¬
structive apnea. The TEB have been
reported as especially common during
obstructive apneic episodes.1721'22 Ob¬
structive apneic episodes are difficult to
identify with the usual clinical recording
method of impedance pneumography.
Using special techniques, Thach and
Stark23 reported that between one third
and half of all apneic episodes were
mixed and obstructive rather than cen¬
tral. Currently, however, there is con¬
troversy as to whether some of the re¬
corded phenomena represent body
movements rather than true apnea.24
Although PB is reported as common,
especially in the least mature infants,
figures for incidence or duration are
rarely included.56,25 Curzi-Dascalova
and Christova-Gueorguieva26 reported
that infants less than 36 weeks of gesta¬
tional age breathed periodically 8.3% of
sleep time, a figure in close agreement
with our own. Results of our study indi¬
cate that the percentage of time spent
breathing periodically by healthy pre-
 term infants may be large and is certain¬
ly highly variable.
While the frequency with which these
cardiorespiratory patterns are seen in
the healthy infant strongly suggests
that they are normal, investigation
of associated physiologic changes is
needed to confirm this. The brief epi¬
sodes of bradycardia are responses to
numerous internal and external stimuli
probably mediated through the vagus.27
Although the majority are not initiated
by hypoxemia,27,28 TEB can be influ¬
enced by the level of oxygénation of the
infant.29 For example, the reflex TEB
associated with sectioning of the tra-
cheobronchial tree can be modified or
eliminated by preoxygenation.30 The ef¬
fects of apnea and TEB on cerebral
blood flow have been reported recently
in very-low-birth-weight infants by
Perlman and Volpe.31 Decreases were
seen in both systolic and diastolic blood
flow when the TEB dropped below 80
beats per minute, suggesting that deep
dips, especially if prolonged or repeti¬
tive, may have pathologic conse¬
quences.
Oxygen levels during periodic
breathing are lower than those during
regular breathing but are still well with¬
in normal levels in healthy infants.6,3Z
Certainly, PB can be induced by rela¬
tive hypoxia and relieved by increasing
ambient oxygen.6,33 In infants with car¬
diorespiratory disease and little re¬
serve, periodic breathing may be an in¬
dication of hypoxia,33 but the clinical
implications of this finding in healthy
preterm infants are unknown.
A relationship with sequelae on fol¬
low-up would also help define the limits
between normal and abnormal cardiore¬
spiratory findings. Surprisingly little
information is available. Butcher-Puech
et al34 showed a relationship between
obstructive apnea in the nursery, intra-
ventricular hemorrhage, positive pres¬
sure ventilation, and abnormal neuro-
development at 1 year; however, these
findings are not necessarily relevant for
healthy infants. The opinion expressed
in the recent National Institutes of
Health (Bethesda, Md) consensus re¬
port was that apnea in the nursery has
little influence on later performance.35
In 1978, the American Academy of
Pediatrics Task Force on Apnea defined
clinically significant apnea as episodes
of 20 seconds or longer or briefer spells
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associated with a TEB.36 The results of
our study do not support the opinion
that brief episodes of apnea are abnor¬
mal when associated with TEB. Apnea
of 15 to 19 seconds associated with drops
in heart rate are common in healthy pre¬
term infants and this association should
not be considered an indication for
treatment or long-term cardiorespira-
tory monitoring. Treatment to eradi¬
cate anormal finding, such as TEB or
PB, can be risky.29 It seems appropriate
for us to remember that administration
of oxygen, which successfully treated
periodic breathing in the healthy pre¬
mature infant, was at least partially re¬
sponsible for the epidemic of retrolental
fibroplasiathat occurred 40 years ago.37
This study was supported by the Zimtbaum Foun¬
dation, New York, NY, The Guild for Infant Sur¬
vival of Orange County, Irvine, Calif, and the Los
Angeles (Calif) Chapter of the National Foundation
for Sudden Infant Death Syndrome.
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