Mixed
and
Obstructive
Sleep
Apnea
and
Near
Miss
for Sudden
Infant
Death
Syndrome:
2.
Comparison
of Near
Miss
and
Normal
Control
Infants
by Age
Christian Guilleminault, MD, Ronald Ariagno, MD, Rowena Korobkin,
MD,
Lynn
Nagel,
PhD,
Roger
Baldwin,
MS,
Susan
Coons,
BA, and
Margaret
Owen,
RN
From the Sleep Research Center and Division of Pediatrics, Stanford University School
of Medicine, Stanford, California
ABSTRACT. Twenty-nine full-term near miss for sudden
infant death syndrome (SIDS) and 30 normal control infants underwent 24-hour polygraphic monitoring.
5ev-eral types of respiratory events during sleep (eg, central, mixed, and obstructive apnea, periodic breathing) were
defined and tabulated. Analysis of these respiratory
van-ables and comparison of groups of near miss and control
infants indicated that between 3 weeks and 4#{189}months of
age only one variable was consistently different at a
statistically significant level: the number of mixed and
obstructive apnea >3 seconds during total sleep time.
This study also showed an increase in mixed and
obstruc-tive respiratory events during sleep at 6 weeks of age in
control as well as in near miss infants. Pediatrics
64:882-891, 1979; sleep, apnea, sudden infant death syndrome,
near miss for sudden infant death syndrome, age group
comparison.
The term “near miss for SIDS” infants was sug-gested in 1963 by Guntheroth’ at the first confer-ence on sudden infant death syndrome (SIDS) to refer to infants with apnea and bradycardia who had experienced an episode of “nearly missed” death and in whom the etiology of the apnea was not apparent.
Over the past six years our understanding of the SIDS victim has evolved, and several reports sug-gest that these infants, as a group, are different from normal infants.2 Although the relationship between near miss for SIDS infants and victims of SIDS is not clear-cut, considerable research and
Received for publication Dec 8, 1978; accepted April 11, 1979.
Reprint requests to (C.G.) Sleep Research Center, TD 114,
Stanford University School of Medicine, Stanford, CA 94305.
PEDIATRICS (ISSN 0031 4005). Copyright © 1979 by the American Academy of Pediatrics.
clinical attention5 has been directed toward the former group, in hopes of learning more about SIDS.
The hypothesis that sleep apnea may play a significant role in SIDS has been considered by several authors including Guntheroth, ‘
Steinschnei-der,6 and our team at Stanford.7 This hypothesis directed attention to the diagnostic and therapeutic enigma of the so-called “near miss” infant. These
infants present a difficult clinical dilemma to the pediatrician. Rational management of their prob-lem is difficult because of the lack of data.
The Stanford University SIDS research program was initiated when the first near miss infant at Stanford was recorded polygraphically in 1972. Since that time 120 infants have been monitored, and many of these infants have been recorded sev-eral times during the first year oflife, as part of this ongoing research program. This report presents the findings from monitoring of respiration during 24 hours in a well-defined population of full-term near miss for SIDS infants and compares age-matched data from normal control infants.
MATERIALS AND METHOD
The parents of the control infants were residents of the San Francisco Bay area community and were
of a lower-middle to upper-middle income bracket and coincidentally equivalent to the range of in-comes among the “near miss” parents. Before inclu-sion in the study, it was ascertained that the family had no known hereditary diseases or family history
of SIDS and that the parents were in good health, that pregnancy and delivery were normal, and that the infant’s growth and development had been within the normal range. Each infant also had a complete physical examination before each record-ing session. All infants were full-term with a mean birth weight of 3,626 (SD ± 380) gm.
The near miss infants reported here also were all
full-term, with a mean birth weight of 3,308 (SD ±
525) gm. Pregnancy and delivery histories were normal. All infants had been discharged in apparent
good health, indicated concomitantly by parental
reports and by hospital and private pediatrician’s medical records. Development was considered
nor-mal until the initial presenting, usually dramatic,
near miss event. All infants had been hospitalized as a result of the “near miss” episode. The parents reported finding the infants colorless or blue, limp,
and not breathing during a time when they were
presumed to be sleeping. Vigorous maneuvers, often
including mouth-to-mouth resuscitation, had been
required before respiration resumed.
When hospitalization and work-up occurred at a medical center other than Stanford, all medical information was obtained and reviewed before the infant’s inclusion into this study. Infants who had a potential etiology, eg, seizure, sepsis, for the near
miss event were eliminated from the study.
Four infants (two boys, two girls) referred for a
near miss event were found to be siblings of SIDS
infants.
Once dassified “near rni&s for SIDS,” 27 of the 29
infants had been placed under a home
cardiorespir-atory monitoring system. Twenty infants
experi-enced a second dramatic event also requiring
vig-orous stimulation and mouth-to-mouth
resuscita-tion. The alarm system alerted the parents and, in
one case, the nursing staff to the infant’s condition.
This second near miss episode usually occurred
within five weeks of the first. All monitored infants
were reported to trigger the alarm at irregular
in-tervals. All had periods during which an increased
number of alarms sounded, but the infants were
TABLE 1. Infant Population and Recordings
Near-Miss Infants Control Infants
Subject
No.
Age at Time of Recording Subject
No.
Age at Time of Recording
3Wk 6Wk 3Mo 4#{189}Mo 6Mo 3Wk 6Wk 3Mo 4#{189}Mo 6Mo
1 X
x
1 X2 X X X X X 2 X X X
3 X X 3 X
4 X X X 4 X
5 X 5
x
X6 X X 6 X
7 X X X 7 X X
8 X X 8 X X X
9 X 9 X
10 X X 10 X X
x
11 X X X 11
x
x
x
12 X X 12 X
13 X X X 13 X X
14 X 14 X X
15 X X 15 X
16 X X 16 X X X
17 X X 17 X
18 X X X 18 X
19 X X X 19 X X
20 X X X 20 X X X
21 X X 21 X X
22 X 22 X
23 X 23 X
24 X 24 X
25 X 25 X
26 X 26 X
27
x
27 X28 X 28 X
29 X 29
30
X
usually found awake and breathing, or normal breathing resumed after gentle shaking (see Table
1).
Procedure
All infants were monitored in the Clinical Re-search Center under similar conditions and an iden-tical experimental protocol. This study was
re-viewed and approved by the Medical Committee for the Protection of Human Subjects in Research, and informed consent of the parents and the ap-proval of the referring pediatrician were obtained. Mothers slept in the research area and were present during the entire procedure and were available to participate in their infant’s routine care. Monitoring lasted for 24 hours with the exception of the eval-uations of three 4’/2-month-old near miss infants that lasted only 12 nocturnal hours. Variables mon-itored during the 24 hours included electroenceph-alogram (C3/A2-C4/A,), electro-oculogram, digas-tric electromyogram, and one electrocardiogram lead (II). Holter ECG was recorded simultaneously for 24 hours. Respiration was measured using sev-eral devices: abdominal and thoracic strain gauges, nasal and oral thermistors, measurement of percent of CO2 in the expired gases through a nasal or oral catheter (Beckman LB CO2 analyzer), and, inter-mittently, an ear oximeter (Waters Instrument Co) to measure oxygen saturation. The infant was under continuous visual observation during the entire monitoring period. Behavior systematically coded on the recording included jerks, twitches, eye move-ments, vocalizations, snores, sucking, gross body movements, etc, during sleep. Artifacts were sys-tematically checked on the recording during the 24-hour period.
Infant Grouping
The dramatic, unexplained “near miss” events occurred at various postnatal ages, and the initial 24-hour recordings, on the average, were done within a week after the reported event. Age groups were determined by the ages at which the first near
miss event was observed by the parents. These
groups are: 3 weeks, 6 weeks, 12 weeks (3 months),
4’/2 months, and 6 months. Control infants were also monitored at these periods between 3 weeks and 6 months of age. Parents usually agreed to return with their infants for follow-up 24-hour monitoring near these specific postnatal ages. Several normal control infants were also recorded more than once, and certain individuals may be presented in more than one age group (Table 1). Thus, it was possible to obtain enough subjects to compare independ-ently each near miss age group to a similar age
group of normal controls. The near miss infants,
who were re-recorded at later age periods, contin-ued to trigger a large number of home monitor
alarms between 3 weeks and 4’/2 months of age, according to parental reporting.
Data Analysis
Respiratory events during sleep were tabulated by type of respiratory pause, ie, central, mixed, obstructive apnea, or periodic breathing. These res-piratory events were defined according to published criteria.8’#{176} Central or diaphragmatic apnea was scored when flat tracings were obtained simultane-ously from strain gauges and thermistors. The curve measuring percentage of expired CO2 was also flat. Obstructive or upper airway apnea was scored when strain gauges exhibited continuous deflections, but no air exchange (flat tracing) was recorded from thermistors. The curve measuring the percentage of expired CO2 was flat in this case also. When the
ear oximeter was in use, simultaneous oxygen de-saturation was observed (Fig 1). Previously pub-lished data,8 obtained using an endoesophageal
pressure transducer, has demonstrated that an
ab-sence of change in pressure (flat tracing) was ob-served when central apnea was scored. Similarly, a progressive increase in endoesophageal pressure with each diaphragmatic movement has been ob-served during obstructive apnea. Mixed apnea was scored when a central apnea was followed by an obstructive apnea or was intermixed with obstruc-tive apnea.9 We must acknowledge that, in our experience, the oral thermistor tracing (or the trac-ing obtained from analysis of the expired CO2 curve when an oral catheter was used) has been flat when the recordings obtained from the nostrils were flat. After six years of multiple sleep monitorings, we
feel that monitoring both nostrils (one thermistor plus a catheter for CO2 pick-up, or two thermistors) is very helpful for pattern recognition of respiratory pauses. The analysis of curves obtained from the thermistors and percentage of expired CO2 has been fairly successful in our hands in defining the differ-ent respiratory events and appears adequate for recognition and differentiation of central, mixed, and obstructive pauses.
Respiratory events were also tabulated by dura-tion: ie, three to six seconds, six to ten seconds, ten to 15 seconds, longer than 15 seconds. Periodic breathing was defined as at least two central events lasting less than ten seconds within 20 seconds of each other.’ ‘ Finally, each event was analyzed as a function of nonrapid eye movement (NREM) sleep, rapid eye movement (REM) sleep, or total sleep time (TST). Sleep was scored by 30-second epochs. At three and six weeks criteria outlined in A
ECG
LEFT NASAL
THERMISTORS I
RIGHT I
THORACIC
ABDOMINAL
--
----S..-.-,
r--I
‘--Control
N#{149}arMiss =
12
10
8
S
4
2
I
C
VI
3 8 3 4.5 6
W..ks Week. Months Months Months
AGE
75uV OBSTRUCTIVE APNEA ;( REM SLEEP
C3 A2
01FF EOG .. .
EMG
I,
STRAIN
GAUGES
5 % EXPIRED C02
0
EAR OXYMETER % 02 90%
Fig 1. Example of repetitive obstructive events in a
3-month-old near miss for SIDS boy during REM sleep.
Note that abdominal and thoracic movements are ob-vious on the tracing, but no air exchange occurs. During each obstructive event, oxygen saturation decreased
(measured by Waters Instrument Co ear oxymeter);
Fig 2. Total mixed and obstructive respiratory events during total sleep time in near miss for SIDS and control
infants plotted using Tukey’s box and whisker
tech-nique.’5”6 A factor 5 was selected to obtain integer values
on the Y axis. The notches around each median indicate a 95% confidence interval based on the standard deviation
Criteria for the Scoring of States of Sleep and
Wakefulness in Newborn Infants’2 were used.
From 3 months of age on, sleep was scored using criteria previously outlined’3 and derived from the
---
---:---- 73%
bradycardia was associated with each apneic event. C3! A2, electroencephalographic electrode placement (from the 10-20 international system); DIFF. EOG, differential
electro-oculogram; EMG, chin electromyogram; ECG, electrocardiogram; REM, rapid eye movement.
from the median. The end of each notch is highlighted by short horizontal tics; these tics give the intergroup com-parison limits at the .05 significance level. This technique allows group comparison and clearly indicates the differ-ence between near miss and control infants, but it also
shows that extreme subjects may overlap.
com-TABLE 2. Respiratory Pauses: 24-Hour Indices
3-6Sec 6-lOSec >10 Sec
Central Mixed Periodic Central . Mixed Periodic Central Mixed
and Breathing and Breathing and
Obstructive Obstructive Obstructive
3Weeks
Near miss n = 10
Control n = 10
R
NR
TST
10.96 ± 3.15
10.01 ± 3.25
5.20 ± 2.16
3.10 ± 1.79 8.78 ± 2.50 6.97 ± 2.44
1.76 ± 2.01
0.38 ± 0.24 0.62 ± 0.55
0.22 ± 0.20 1.28 ± 1.32
0.31 ± 0. 18
8.65 ± 5.47
10.54 ± 8.61
3.81 ± 3.60
4.68 ± 5.82
6.69 ± 4.46
7.43 ± 7.05
3.12 ± 1.98
3.07 ± 0.89
2.67 ± 2.29
2.50 ± 0.44
3.11 ± 1.92
2.87 ± 0.45
1.49 ± 1.17
0.29 ± 0.24
0.57 ± 0.48
0.18 ± 0.30
1.11 ± 0.81
0.24 ± 0.26
2.99 ± 3.39
4.13 ± 5.60
2.50 ± 2.99
3.46 ± 5.35
2.91 ± 3.07
3.69 ± 5.08
0.24 ± 0.34
0.50 ± 0.56 0.67 ± 0.89
0.91 ± 1.09
0.50 ± 0.59
0. 73 ± 0. 72
022 ± 0.45
0.05 ± 0.08
0.21 ± 0.30
0.06 ± 0.08
0.23 ± 0.39
0.07 ± 0.09
6Weeks
Near miss n = 7 Controln=10
R
NR
TST
13.76 ± 426
9.85±2.59
6.48 ± 2.71
4.29±1.97
10.05 ± 3.01
7.10 ± 1.57
2.38 ± 1.77
0.98±1.43
0.86 ±0.62
0.37±0.21
1.56 ± 1.09
0.66 ± 0.66
13.60 ± 16.20
7.89±8.03
10.16 ± 13.28
4.12±6.23
12.33 ± 14.41
6.11 ± 7.15
3.64 ± 1.73
2.70±1.58
3.29 ± 1.64
1.97±0.97
3.57 ± 1.55
2.46 ± 1.15
1.85 ± 1.57
0.49±1.05
1.21 ± 1.63
0.29±0.39
1.54 ± 1.47
0.38 ± 0.61
4.12 ± 6.41
1.84±2.79
3.97 ± 4.42
4.42±10.28
4.29 ± 4.90
3.26 ± 6.45
0.39 ± 0.61
0.07±0.21
0.73 ± 1.05
0.60±1.19
0.61 ± 0.89
0.36 ± 0.66
0.28 ± 0.51
0.11±0.31
0.51 ± 0.99
0.08±0.14
0.44 ± 0.84
0.10 ± 0.21
3 Months
Near miss n= 15 Controln=9
R
NR
TST
9.74 ± 5.18
11.20±4.84
3.39 ± 1.52
3.09±1.09
6.03 ± 2.87
6.08 ± 2.28
1.30 ± 1.18
0.48±0.74
0.48 ± 0.69
0.11±0.18
0.83 ± 0.82
0.28 ± 0.46
15.24 ± 14.09
7.56±2.82
3.10 ± 3.43
1.08±0.73
7.68 ± 6.70
3.43 ± 1.08
2.54 ±2.21
2.66±2.22
1.83 ± 1.09
1.78±1.05
2.10 ± 1.33
2.18 ± 1.49
0.56 ± 0.37
0.24±0.29
0.27 ± 0.23
0.06±0.08
0.39 ± 0.26
0.13 ± 0.13
3.66 ± 4.68
1.54±1.52
1.75 ± 2.28
0.53±0.37
2.44 ± 2.87
0.93 ± 0.58
0.08 ± 0.20
0.10±0.21
0.39 ± 0.77
0.18±0.18
0.28 ± 0.55
0.16 ± 0.19
0.07 ± 0.09
0.06±0.12
0.06 ± 0.10
0.06 0.06
0.07 ±0.07
0.02 ± 0.05
4#{189}Months Near miss n = 13 Control n= 10
R
NR
TST
13.13 ± 2.94
9.64 ± 3.52
3.70 ± 2.10
2.52 ± 1.22
6.92 ± 1.86
4.80±1.53
0.96 ± 1.08
0.26 ± 0.30
0.45 ± 0.64
0.10 ± 0.16
0.64 ± 0.80
0.15±0.21
18.54 ± 16.14
17.1 7 ± 4. 75
4.55 ± 9.24
0. 70 ± 0.81
9.36 ± 11.32
2.67±1.76
2.65 ± 1.74
1.54 ± 1.1 7
1.58 ± 1.03
1. 15 ± 0.97
1.96 ± 0.97
1.31±0.93
0.49 ± 0.64
0.15 ± 0.23
0.12 ± 0.15
0.02 ± 0.06
0.24 ± 0.21
0.07±0.11
4.78 ± 4.74
1.26 ± 0.85
1.85 ± 3.74
0.25 ± 0.33
2.89 ± 2.86
0.57±0.45
0.15 ± 0.25
0.05 ± 0.10
0.26 ± 0.36
0.34 ± 0.48
0.22 ± 0.32
0.24±0.32
0.07 ± 0.14
0.06 0.00
0.01 ± 0.04
0.00 0.00
0.31 ± 0.07
0.00 0.00
6Months
Near miss n = 12
Control n = 9
R
NR
TST
-11.68 ± 3.79
10.96 ± 3. 79
2.48 ± 1.66
2.31±0.96
5.23 ± 2.46
4.77± 1.35
0.64 ± 0.86
0.38 ± 0.69
0.15 ± 0.29
0.07±0.09
0.29 ± 0.43 0.17 ± 0.24
10.95 ± 9.43
12.63 ± 9.97
1.87 ± 2.66
0.95±1.01
4.54 ± 4.63
4. 16 ± 2.96
3.09 ± 1.73
2.81 ± 2. 1 1
2.04 ± 1.34
2.16±1.02
2.35 ± 1.40
2.34 ± 0.93
0.44 ± 0.74
0.09 ± 0.19 0.08 ± 0.14
0.00±0.00
0.19 ± 0.31
0.03 ± 0.05
3.18 ± 3.18
2.54 ± 2.09 0.83 ± 1.21
0.45±0.4.5
1.53 ± 1.66
1.01 ± 0.65
0.31 ± 0.58
0. 14 ± 0.30
0.49 ± 0.61
0.28±0.32
0.44 ± 0.53
0.25 ± 0.30
0.08 ± 0.18
0.00 0.06
0.01 ± 0.03
0.00 0.06
0.03 ± 0.06
0.00 0.00
S The table presents the mean (and standard deviations from the mean)numberofrespiratory pauses during sleep during the
24-hour period for each age group. The apnea index used is equal to the number of respiratory events, divided by sleep time, multiplied
by 60 (60 minutes). Abbreviations used are: R, rapid eye movement sleep; NR, nonrapid eye movement sleep; TST, total sleep time;
, mean.
puted by dividing the number of respiratory events by the amount of sleep time in minutes and multi-plying by 60 (Index = No. of respiratory events
-‘-sleep time x 60). This yielded an index of specific
types of apnea per sleep-hour. Infants were
system-atically awakened and stimulated if apnea reached
30 seconds, or 20 seconds with severe bradycardia. Therefore, no apneas longer than 30 seconds were
recorded.
Statistical Analysis
In comparing single respiratory parameters
across age groups, a proportional relationship
be-tween mean and standard deviation was found. A
logarithmic transformation [in (x
+
1)] was per-formed on each apnea index to suppress this effect,making the data more normally distributed and
amenable to statistical treatment. The logarithmic
argument (x
+
1) allowed zero values to be includedin the transformation.
The large number of parameters being monitored
increased considerably the probability of having a
nonhomogeneous subject population with respect to any given parameter. This may decrease the credence of some numerical treatments. The anal-ysis suggested by Tukey15 permits a convenient characterization of overall group behavior for each respiratory parameter. (An example of the use of
this technique can be seen in Fig 2 below: the
median value (50th percentile), the interquartile range (25th to 75th percentiles), and the upper and lower extremes are plotted for each group.) This analysis clearly distinguishes the extremes (out-hers) from the bulk of the population (interquartile
= 25th to 75th percentile). It also shows the extent
> 15 Sec Total Periodic
Breathing
Total Pause s (Central, Mixed and Obstructive) Total Pauses
Mixed
Central Mixed >3 Sec >6 Sec >10 Sec
and and
Obstructive Obstructive
0.00 0.00 0.03 ± 0.10 11.65 ± 8.59 29.46 ± 13.88 8.09 ± 6.40 0.49 ± 0.83 3.49 ± 2.99
0.00 0.00 0.00 0.00 14.66 ± 14.04 28.97 ± 16. 79 8.04 ± 6.02 0.56 ± 0.61 0. 73 ± 0.42
0.02 ± 0.05 0.03 ± 0.06 6.31 ± 6.48 16.29 ± 10.70 6.66 ± 5.67 0.92 ± 1.04 1.42 ± 1.04
0.00 0.00 0.00 0.00 8.13±11.07 15.99±13.09 7.10±6.51 0.97±1.15 0.45±0.44
0.01 ± 0.02 0.04 ± 0.10 9.59 ± 7.38 24.65 ± 11.56 7.90 ± 5.68 0.78 ± 0.89 2.66 ± 2.03
0.00 0.00 0.00 0.00 11.12±12.04 22.31±14.59 7.60±5.84 0.80±0.79 0.62±0.40
0.02 ± 0.06 0.11 ± 0.30 17.71 ± 22.29 40.14 ± 25.22 10.41 ± 7.88 0.80 ± 1.17 4.62 ± 3.43
0.00 0.00 0.03 ± 0.10 9. 72 ± 10.78 23.95 ± 15.25 5.23 ± 5.38 0.2! ± 0.61 1.61 ± 2.87
0.12 ± 0.33 0.43 ± 1.12 14.13 ± 17.66 27.75 ± 21.19 10.26 ± 7.88 1.79 ± 3.27 2.10 ± 4.05
0.00 0.00 0.00 0.00 8.53 ± 16.47 16.12 ± 17.59 7.35 ± 11.45 0.68 ± 1.20 0.74 ± 0.57
0.09 ± 0.25 0.30 ± 0.79 16.62 ± 19.19 13.77 ± 22.58 10.83 ± 7.54 1.44 ± 2.49 3.83 ± 3.66
0.00 0.00 0.01 ± 0.04 9.37 ± 13.50 20.45 ± 15.54 6.58 ± 7.98 0.48 ± 0.78 1.16 ± 1.49
0.00 0.00 0.00 0.00 18.89 ± 18.13 33.18 ± 21.25 6.91 ± 5.40 0.15 ± 0.24 1.93 ± 1.45
0.00 0.00 0.00 0.00 9.10 ± 3. 73 23.84 ± 8.66 4.60 ± 3.38 0. 16 ± 0.31 0. 78 ± 0.81
0.00 0.00 0.01 ± 0.03 4.85 ± 5.55 11.28 ± 6.78 4.30 ± 3.12 0.46 ± 0.80 0.81 ± 0.95
0.00 0.00 0.00 0.00 1.61±0.92 6.75±1.85 2.55±1.38 0.18±0.18 0.17±0.20
0.00 0.00 0.01 ± 0.03 10.13 ± 9.25 19.83 ± 11.43 5.29 ± 3.66 0.35 ± 0.58 1.30 ± 1.06
0.00 0.00 0.00 0.00 4.36±1.48 13.21±4.35 3.42±2.17 0.18±0.23 0.43±0.49
0.00 0.00 0.00 0.00 23.32 ± 20.75 40.77 ± 22.73 8.14 ± 5.98 0.22 ± 0.34 1.52 ± 1.45
0.00 0.00 0.00 0.00 8.44±5.42 20.07±8.81 2.99±1.87 0.05±0.10 0.40±0.50
0.00 0.00 0.00 0.00 6.40 ± 12.96 12.53 ± 14.80 3.83 ± 434 0.27 ± 0.38 0.58 ± 0.74
0.00 0.00 0.00 0.00 0.95±1.09 5.09±3.32 1.76±1.58 0.35±0.49 0.13±0.23
0.00 0.00 0.00 0.00 12.25 ± 15.16 22.27 ± 17.05 5.34 ± 4.68 0.26 ± 0.37 0.92 ± 0.93
0.00 0.00 0.00 0.00 3.24 ± 2.12 9.81 ± 4.40 2.19 ± 1.64 0.24 ± 0.34 0.23 ± 0.32
0.00 0.00 0.00 0.00 14.14 ± 12.80 30.38 ± 19.29 7.10 ± 5.92 0.39 ± 0.72 1.16 ± 1.65
0.00 0.00 0.00 0.00 15.17±11.73 29.55±16.47 5.58±4.13 0.14±0.30 0.47±0.81
0.00 0.00 0.00 0.00 2.70 ± 3.78 7.95 ± 6.41 3.46 ± 2.60 0.50 ± 0.60 0.24 ± 0.42
0.00 0.00 0.00 0.00 1.41±1.42 6.24±2.49 2.91±1.24 0.29±0.32 0.07±0.09
0.00 0.00 0.00 0.00 6.08 ± 6.22 14.61 ± 9.99 4.54 ± 3.37 0.47 ± 0.55 0.51 ± 0.76
0.00 0.00 0.00 0.00 5.1 7 ± 3.52 12. 73 ± 5.09 3.63 ± 1.49 0.25 ± 0.30 0.20 ± 0.27
allows for the degree to which normality of the distribution is to be expected. The same factor is used in all plots, and its value is such that non-overlap of the notches (the ends of which are high-lighted by short horizontal bars or “tics”) between any two groups infers a significant difference at the
P : .05 level, provided the distribution of data is not extremely
Finally, the groups at each age were compared using both the two-tailed Student’s t- and the Mann-Whitney U-tests.
RESULTS
Table 2 shows the means and standard deviations of the 24-hour sleep-related respiratory pauses for each age group (control and “near miss”), and Table 3 presents the results of the statistical analysis for each age group. When near miss for SIDS and normal control infants were compared, the number of mixed and obstructive apneas was the only res-piratory event during sleep significantly different,
up to 4#{189}months of age. Fig 2 shows the total mixed and obstructive apnea data during total sleep time in the control and near miss subjects at different age groupings (3 weeks, 6 weeks, 3 months, 4#{189} months, and 6 months). The exploratory analysis technique was used for visual presentation of the obtained data. Group differences were minimal by 6 months of age.
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No statistical difference was demonstrated when the total sleep time of control and near miss infants
was compared between 3 weeks and 4#{189}months (Table 4). There was a statistically significant dif-ference at 6 months of age. Near miss infants slept longer than controls, but the use of the apnea index allowed us to compare adequately the respiratory
events of the two groups at 6 months.
Although the normal and near miss for SIDS infants showed statistically significant group
differ-ences, the number of mixed and obstructive events
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Fig 3. Mean (±SD) total number of mixed and obstruc-tive respiratory events longer than three seconds in near
miss for SIDS and control infants during rapid eye
move-ment (REM) sleep (top) and during nonrapid eye move-ment (NREM) sleep (bottom). Both groups had an in-crease during both REM and NREM sleep near 6 weeks
of age and a subsequent progressive decline, reaching the lowest level near 6 months. The breaks in the graph
between 6 weeks and 3 months indicate that the tech-nique for staging sleep was switched from the classic newborn manual’2 to another technique’3 that better indicates the infants’ progressive maturation.
peaked in both groups at 6 weeks of age, in
com-parison to the numbers observed at 3 weeks and at
3 months. This age-related change can be seen in Fig 3. The graphic representations of the means (and standard deviations from the mean) of the total number of mixed and obstructive respiratory events in NREM sleep and REM sleep show that this increase was neither limited to the near miss infants, as it was also observed in the control group, nor was it related to a specific sleep state. The mean (±SD) mixed and obstructive apnea index de-creased with age after that peak and became very low at 6 months.
DISCUSSION
In this study we investigated the respiratory
pat-terns during different states of sleep of “near miss”
infants compared to normal control infants between 3 weeks and 6 months of age. We tried to differen-tiate the two groups by differences in polygraphic variables. The validity of these differences rests on the clear clinical distinction between near miss and control infants. We have attempted to define the population of near miss infants to make them as homogeneous a group as possible. Considerable at-tention was given to standardization of collection of data; several years of continuous monitoring are represented in the reported results. We eliminated premature infants from our analysis, despite the fact that near miss for SIDS and SIDS infants are often premature, because of our concern about in-creasing the number of uncontrolled variables.
Each infant group, except the group of 3-week-old infants, was partially composed of subjects
pre-+NEAR-MISS viously recorded at an earlier age, as shown in Table
CONTROL Although we initially recorded the near miss
infants within a short period of time after the first
reported event, it is possible that some of these infants had had previous long sleep apneas unno-ticed by their caretakers.
We have included in the 4’/2 month old near miss infant group three infants who were recorded for only 12 nocturnal hours at parental request. The use of the apnea index (number of apneas per sleep-hour) allowed us to add these data to those obtained from the 24-hour studies. We felt that the addition of more data points strengthened the statistical analysis. Even if these three cases are excluded, the total number of mixed and obstructive apneas dur-ing total sleep time is statistically significant (P .05).
In the near miss group some infants had isolated polygraphic abnormalities, such as an episode dur-ing sleep of central apnea up to 30 seconds with severe cardiac arrhythmia. In this study, however, in which the near miss infants were carefully
any, doubt existed about the occurrence of the
event, observations of long (ie, 15 second) apneas were rare and too few for valid statistical analysis.
on
examining the respiratory data, we were sur-prised to find so few polygraphic differences be-tween near miss and control groups. Total number of central apneas, number of apneas greater than10 seconds, amount of periodic breathing, and total sleep time (until 4#{189}months of age) were similar in both groups. The number of mixed and obstructive respiratory pauses during total sleep time in near
miss infants was the only consistently significant variable compared to controls. The duration of these events was usually fairly short, but their amount was greatly increased. In one near miss infant who died of SIDS within 36 hours after the recording, the large total number of mixed and obstructive respiratory pauses during total sleep
time was the only significant abnormality noted in a 24-hour polygraphic monitoring.’7 We have
men-tioned that 20 near miss for SIDS infants out of the
29 studied experienced a second dramatic event, necessitating vigorous resuscitation by the parents, but, based on our recording data, we were unable to differentiate this subgroup from the nine remaining infants at the time of the first monitoring.
Greater attention should be given to mixed and obstructive apneas during sleep, and our positive and negative findings support the concept that su-perficial polygraphic screening of near miss infants, based solely upon recording of thoracic and abdom-inal movements, frequently is not discriminatory and is not helpful when negative for prolonged
apnea.
It may be suggested that combining mixed and obstructive apneic events in our tally is misleading and will not help us better undeistand the primary mechanism responsible for the increase in these abnormal respiratory events during sleep. We ac-knowledge the validity of this criticism: we do not
know where the obstruction occuis, or to what it is related. It has recently been demonstrated that abnormal esophageal reflux is involved in some SIDS 18 and one could argue that obstruction
is secondary to pharyngeal secretion entering the laryngeal areaS Similarly, obstruction of the nostrils in obligate nose breathers may be an important factor for some infants. Mixed and obstructive ap-neas were linked together because of the clinical impact of the obstructive component,9 most fre-quently ignored. Although the sequence of an ob-struction preceding a central apnea is theoretically possible, we have never observed this during our multiple recordings. Thus, the question of why there is a dissociation between diaphragmatic movements (central apnea) and upper airway open-ing, as seen in mixed apnea, needs explanation. This
phenomenon has been well documented in chil-dren’9 and adults#{176} with the sleep apnea syndrome, but there too the basic underlying mechanisms are unclear. Further evaluation of the obstructive event is necessary to understand the pathophysiology of
the near miss event.
The observed increase of mixed and obstructive
pauses at 6 weeks of age during NREM and REM
sleep in both near miss and control infants, we feel, deserves attention. Various groups223 have noted a fairly large variation among infants in number of apneic events. The large standard deviations noted clearly confirms this. Hoppenbrouwers et al,2’ Gould et al, and Monod et a!23 have found that apnea density decreased during active (REM) sleep from 1 week to 4 to 6 months of age in their normal,
full-term infants. The apnea density reported dur-ing quiet (NREM) sleep was low, and none of these
authors mentioned a peak near 6 weeks of age. Two factors may be responsible for this discrepancy: (1) In their published results, none of these authors
differentiated central, mixed, and obstructive apnea (for comparison see Fig 3); (2) Hoppenbrouwers et
a!,2’ who obtained the greatest number of data points during the first 6 months of life, monitored their infants at 1, 2, 3, 4, 5, and 6 months and may have missed an increased number of events near 6
weeks of age because of their study design.
Finally, since the majority of near miss events
occur in a home setting, home recordings may yield information unavailable in the sleep laboratory. We prescribe home monitors, as do Steinschneider,24 Kelly et al,5 and other groups, not only to obtain data but in the hope of protecting the infant from subsequent events. From our findings, however, we
feel that equipment that records only thoracic and abdominal respiration is inadequate for a high level of confidence. The fact that in mixed apneas the central component has consistently occurred first in our polygraphic monitoring, further underlines the risk of using home monitors based only on thoraco-abdominal movements.
ADDENDUM
Since this article was submitted several papers relevant
to the data presented here have been published. In Jan-uary 1979, Peabody et al25 reported a different technique
than that presented here to monitor obstructive apnea in near miss for SIDS infants. They remarked also, as we have,8 on the problems inherent in recording only thoracic and abdominal movements and the inadequacy of such a limited recording technique. The cutaneous Po elec-trode, when its accuracy-particularly in older infant groups-has been confirmed by further studies, may be
helpful in assessing an infant’s risk in the hospital and at
home.
of the posterior pharyngeal wall and backward movement of the tongue and lower jaw. This is similar to
observa-tions reported in older children and adults27’ with ob-structive sleep apnea syndrome. This report is very
inter-esting in that information previously obtained from
elec-tromyographic recordings of the genioglossus and other
muscles involved in the control of the oropharynx in
adults and older children could be applicable to infants
as well.
Finally, Kelly and Shannon#{176} reported that periodic breathing during sleep was statistically different when they compared full-term near miss vs full-term control infants using a home monitoring device. Our findings
differ. As mentioned in the text, we found periodic
breath-ing very common in normal controls (with large standard deviations); it may, in fact, occur throughout several hours of sleep. Duration of recordings and type of
moni-toring (laboratory-controlled vs home monitoring using
an impedance apnea monitor) may partially explain this difference. Clearly, more normative data must be
ob-tamed before we can fully understand the frequency and
significance of periodic breathing.
ACKNOWLEDGMENTS
This research was supported in part by National Insti-tute of Child Health and Human Development grant HD
08339 and National Institutes of Health grants RR-70
and RR-81 from the General Clinical Research Centers
Program, Division of Research Resources; and by IN-SERM to Dr Guilleminault.
The authors thank Dr Helena Kraemer for advice on
the statistical analyses.
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