Sleep, 16(5):409-413
© 1993 American Sleep Disorders Association and Sleep Research Society
Pediatric Clinical Research
Clinical Symptoms Associated With Brief
Obstructive Sleep Apnea in Normal Infants
*A. Kahn, *1. Groswasser, *M. Sottiaux, *E. Rebuffat,
*M. Sunseri, tP. Franco, tM. Dramaix, :j:A. Bochner,
§B. Belhadi and §M. Foerster
*Pediatric Sleep Unit, University Children's Hospital, Free University of Brussels,
tUniversity Clinic Erasme, tUI Antwerpen and §Institut Edith Cavell, Brussels, Belgium
Summary: Relatively little data exist concerning the manifestations of repeated obstructive sleep apnea in normal
infants. A questionnaire concerning daytime and sleep habits was completed by the parents of 4, I 00 healthy infants
before they underwent a 9-hour night monitoring study. One hundred infants with an obstructive apnea index
above 1.2 were randomly selected. They formed the "apnea" group. From the initial population, 300 infants with
no apnea were also selected to form the "no-apnea" group. Both groups were matched for sex, gestational age, post
conceptional age, birth weight, mother's age, parity and a family history of sudden infant death. Five variables
from the questionnaires significantly differentiated the two groups of infants. When awake, the infants with apnea
were characterized by a greater frequency of breathholding spells (22% of apnea infants) and episodes of fatigue
during feeding (28%) than the non-apnea infants. During sleep, they exhibited a greater frequency of profuse sweating
(15%), snoring (26%) or noisy breathing (44%). Multiple symptoms were present in some infants. A stepwise logistic
regression resulted in two significant independent variables: profuse sweating during sleep (p = 0.008) and noisy
breathing (p = 0.002). The predictive value of these two symptoms was tested on a new group of 650 healthy
infants. The two independent variables led to the correct classification of 60 of the 67 infants with apnea (89.67%)
and 382 of the 583 non-apnea infants (65.5%). A positive history alone had a positive predictive value of 0.21. A
history of profuse sweating and noisy breathing during sleep in the absence of an upper respiratory infection could
contribute to identifying infants with obstructed breathing episodes during sleep. Key Words: Sleep-SnoringSweat-Apnea-Obstructive apnea.
Symptoms associated with the presence of repeated
obstructive sleep apneas have been reported in children with upper airway abnormalities, such as Pierre
Robin syndrome or choanal atresia. These manifestations include snoring, respiratory distress, cyanosis
or apneic spells (1-5).
Repeated obstructive sleep apneas may also be found
in apparently normal infants (4-11). Little is known
about their clinical manifestations, although a description of apnea-related symptoms could be useful for the
clinician studying normal infants (1,5,6,8,11).
Accepted for publication March 1993.
Address correspondence and reprint requests to A. Kahn, Pediatric
Sleep Unit, University Children's Hospital Reine Fabiola, avo J.J.
Crocq IS, B-1020 Brussels, Belgium.
"
The aim of the present study was to investigate
whether specific symptoms are associated with the
presence of obstructed sleep apneas in apparently
healthy infants.
MATERIALS AND METHODS
Patients
From January 1986 to September 1991, a multicenter prospective study was conducted to collect normative data on sleep and cardiorespiratory characteristics of infants. The four pediatric sleep laboratories
were located in urban areas and admitted subjects from
all socioeconomicallevels. A total of 4,100 infants with
409
410
A. KAHN ET AL.
a median age of9 weeks (range 4-25 weeks) were studied. All infants were healthy, receiving no medication,
had no history of sleep apnea and no history of sudden
infant death syndrome (SIDS) in the family. For each
infant, an investigator interviewed one or both parents
to complete a standardized questionnaire before the
infants' sleep was studied.
Questionnaires
Questionnaires listed 50 questions related to the
family's medical history, the infant's prenatal and postnatal history, as well as the infant's behavior while
awake and asleep. Questions relating to apneas were
based on out clinical experience and the available literature. All questions were explained to the parents.
"Breathholding spells" included blue or white spells,
with or without loss of consciousness, that occurred
while or after the infant was crying (5). "Fatigue during
feeding" referred to the infant who choked, became
exhausted, who stopped drinking and remained dyspneic and panting for some time before feeding could
resume. "Noisy breathing" during sleep was defined
as a respiratory noise, other than "snoring" or "stridor", that was noticed at a time the infant had no
airway infection. "Sweating during sleep" was graded
by the parents as absent, mild (drops of sweat on the
infant's head), moderate (bed sheet under the infant's
head moist with sweat) or profuse (pyjamas and/or bed
sheets soaked with sweat). Parents were also asked how
many nights per week the symptoms were noticed. The
questionnaires were initially tested on a pilot sample
of 70 infants, and because of obvious misunderstandings, some questions were modified. The modified
questionnaires were satisfactorily evaluated by a new
group of 30 families.
Polygraphic studies
After the histories were obtained, the infants were
admitted for a 9-hour night monitoring session. They
were observed continuously during recordings, and their
behavior and vocalization, as well as nursing interventions, were charted. All patients slept in their usual
sleep position, without restraints, and care was taken
to avoid neck flexion. The data was collected on standard polygraph recorders (10 mm/second paper speed).
The following variables were simultaneously recorded:
scalp electroencephalogram (EEG), electrooculogram
(EOG), digastric electromyogram (EMG) electrocardiogram (EKG), thoracic and abdominal respiratory
movements by strain gauges and airflow by thermistors
taped under each nostril and on the side of the mouth.
Oxygen saturation was recorded continuously from a
transcutaneous sensor (Nellcor). Thirty-second periods
Sleep, Vol. 16, No.5, 1993
of the recordings were analyzed and categorized as either nonrapid eye movement sleep (NREM), rapid eye
movement sleep (REM), indeterminate sleep or wakefulness according to the criteria recommended in the
literature (12, 13). Apneas were scored only if they lasted ::::3 seconds (6-11). Central apnea was scored when
flat tracings were obtained simultaneously from the
strain gauges and the thermistors. An obstructive apnea was scored when continuous deflections were obtained from the strain gauges and a flat tracing was
recorded from the thermistors. To avoid artifactual
scoring of obstructive events due to displacement of
the thermistors, any doubtful episodes (such as obstructed breathing preceded by a movement or a sigh)
were rejected. Mixed apneas were defined as a central
apnea directly followed by an obstructive episode, their
duration being additive. Obstructed breathing events
included both obstructive and mixed apneas. An apnea
index represented the total number of obstructive
breathing events per hour of sleep. The total number
of events was divided by the total sleep time and multiplied by 60. Two independent scorers analyzed the
sleep recordings to ensure reliability. Interrater agreement was 86%. Scoring discrepancies were discussed
and codes thus agreed upon were used in the data
analysis.
Data analysis
The study was performed in two steps. First, from
the 4, 100 sleep recordings performed following the research protocol, 100 infants with an obstructive apnea
index above 1.2 were randomly selected. Their apnea
index was greater than the 97th percentile for obstructive breathing events reported for normal infants of
the same age group (4-11). They formed the "apnea"
group. From the initial population of 4,100 subjects,
300 infants with no obstructive events were also selected. They matched the apnea infants for sex, gestational and postconceptional age, birth weight, mother's age and parity. They formed the no-apnea group.
The responses to the questionnaires were compared
for the two groups by single-variable comparisons with
the use of Fischer exact test for nominal variables or
Wilcoxon Rank test for continuous variables. The level
of significance was p < 0.05. A stepwise logistic regression (SPSS, Release 4.0) was then performed to
allow the best classification of independent symptoms.
Second, to validate the initial findings, a new group
of 650 healthy infants were randomly selected from
the initial population of 4,100 subjects. The infants
were studied with the methodology described above
in order to confirm that the selected symptoms led to
their appropriate classification.
-
- - - - - - -
OSA IN INFANTS
411
TABLE 1. Main polygraphic characteristics of the infants. REM sleep refers to rapid eye movement sleep and NREM sleep
to nonrapid eye movement sleep. The figures represent absolute, median and range values
Apnea
group
No. of infants
Gender (M/F)
Gestational age (wk)
Birth weight (g)
Mother's age (years)
Rank in the family
Age at study (weeks)
Polygraphic studies:
Obstructive apneas
No.
Seconds
Apnea index (No. per hour)
Heart rate below 100 c.p.m.
Central apneas (seconds)
Periodic breathing (Ofo)
REM sleep (%)
NREM II-III sleep (%)
No. of awakenings
Total sleep time (hours)
100
No-apnea
group
p
300
64/36
195/105
39 (37-41)
3,213 (2,960-4,385)
28 (17-38)
2 (1-3)
9.5 (5-18)
39 (37-41)
3,310 (2,870-4,280)
28 (18-40)
2 (1-5)
9.2 (5-20)
12 (8-16)
10 (3-13)
1.4 (1.2-1.8)
56179
9 (5-22)
0(0-10)
29 (20-39)
47 (23-59)
5 (1-10)
8.5 (6.5-9.2)
ns
ns
ns
ns
ns
ns
o
271298
9 (3-15)
0(0-8)
31 (22-35)
50 (23-63)
4 (0-9)
8.0 (6.0-9.7)
.001
ns
ns
ns
ns
ns
ns
Noisy breathing, snoring and excessive sweating were
all found in these eight infants.
Most of the variables studied did not differentiate
the apnea from the no-apnea subjects. During wakefulness, similar frequencies were found for episodes of
RESULTS
choking or sweating during feeding, postprandial regurgitation, body weight and height or history of upper
The descriptive analysis by single-variable
respiratory tract infections.
comparisons
For the infants of both groups, similar values were
reported
for the duration of nighttime sleep (median
Because of our study design, the polygraphic studies
=
9.2
hours;
range = 8.8-10.5 hours), total daytime
significantly differentiated the two groups of infants,
1.5 hours; range 0-2.5 hours), number
sleep
(median
but no difference existed for any of the following variof
nighttime
awakenings
(median 1; range 0-4), epiables: mother's age and parity, sex of the infant, gesof
pallor
(20%
and
24% for the apnea and nosodes
tational age or birth weight (Table 1). The obstructive
apneas had a median duration of 10 seconds and were apnea groups, respectively) or cyanosis (3% and 1%
accompanied by a median drop in heart rate of 19% for the apnea and no-apnea groups, respectively).
Some symptoms were rarely, if ever, reported in the
of the initial heart rate value. Obstructive apneas lasttwo
groups of infants, such as apnea, coughing or aging 10 seconds or more were found in eight infants;
itation
during sleep, day-time fatigue or hyperactivity.
three infants had apneas between 15 and 21 seconds.
Family histories showed no significant differences in
the frequency of profuse night sweating, breathing difT ABJ"E 2. Significant symptoms differentiating the two ficulties or parental cigarette smoking.
groups of infants. The figures represent absolute values and
Only five symptoms significantly differentiated the
(percents)
two groups (Table 2). When awake, the apnea infants
Apnea
No-apnea
were characterized by a greater frequency of breathgroup
group
holding spells (22% of subjects). The spells were dep
No. (%)
No. (%)
scribed as blue or white, and no infant loss conscious100
300
No. of infants
ness. The apnea infants were also characterized by
During wakefulness
episodes offatigue during feeding (28% of infants), with
48 (16)
0.006
22 (22)
Breathholding spells
repeatedly interrupted sessions of breast (eight infants)
48 (16)
0.001
28 (28)
Fatigue during feeding
or bottle feeding (20 infants). During sleep, the apnea
During sleep
infants
exhibited profuse sweating (15% of subjects),
21 (7)
0.010
15 (15)
Profuse sweating
68 (23)
0.045
26 (26)
snoring (26%) and noisy breathing (44%). More than
Snoring
0.001
75 (25)
44 (44)
Noisy breathing
one symptom were present in some infants. For in-
The University Ethical Committee had given its approval to the study, and informed parental consent was
obtained.
Sleep, Vol. 16, No.5, 1993
412
A. KAHN ET AL.
stance, profuse night sweating was found together with TABLE 3. Logistic regression procedure based on the five
noisy breathing (28%), fatigue during feeding (26%), significant symptoms for obstructive sleep apneas. B = logistic
regression coefficient; SE = the coefficient standard deviation;
snoring (22%) or breathholding spells (15%).
Sig = coefficient level of statistical significance; Exp = coefA stepwise logistic regression with the five significant
ficient exponential value
symptoms resulted in two significant independent variVariables
Sig
B
SE
Exp (B)
ables: noisy breathing (p = 0.002) and profuse sweating
During sleep
during sleep (p = 0.008) (Table 3).
The validation study
Following sleep analysis, 583 of the 650 subjects
randomly selected for the validation study formed a
no-apnea group and 67 an apnea group (10.3% of infants). The combination of the two independent variables led to the correct classification of 60 of the 67
apnea infants (89.6%), and 382 of the 583 no-apnea
infants (65.5%). Identification of apnea subjects was
obtained with a sensitivity of 0.90, a specificity of 0.66
and a positive predictive value of 0.21.
DISCUSSION
Three caveats should be acknowledged when interpreting our data. First, our definition of obstructive
apneas in infants is less stringent than that used for
older children or adults (14,15). Most authors concur
that criteria should be adapted to the age of the patient
(15-19), especially when obstructions per se do not
imply pathology (19). Second, the symptoms studied
are by their nature subjective and their interpretation
could be misleading. We cannot exclude the possibility
of parental bias in the reporting of the behavior of their
infant, despite our efforts to explain the questions and
to obtain more quantitative answers. This potential
bias is reduced by the use of the same questionnaires
for both the apnea and the control subjects. Third,
because of our study design, some major questions on
sleep apneas were not addressed. We did not control
for the possible presence of hypopneas (1,17), or increased upper airway loads (18), as we did not quantitatively evaluate ventilation (15,20). Differences in
these variables could have modified the interpretation
of our findings. Neither did we investigate the causes
for the development of obstructed breathing events in
our infants. Both anatomic and physiologic factors
could precipitate sleep apnea in otherwise normal infants (1,18,21-23).
With these limitations in mind, five markers for obstructed sleep apnea in otherwise healthy infants were
found; breathholding spells, fatigue during feeding,
snoring, noisy breathing and profuse sweating during
sleep. These symptoms have occasionally been associated with sleep apnea. Infants with "breathholding
spells" have been reported to have a higher incidence
of obstructive sleep apnea (5). "Fatigue during feeding"
Sleep, Vol. 16, No.5, 1993
Profuse sweating
Noisy breathing
Constant
1.106
0.S56
-1.772
0.416
0.275
0.IS2
O.OOS
0.002
3.02
2.35
has been associated with abnormal coordination of
breathing and swallowing during sleep (3,24). "Profuse
sweating" during sleep has been described in infants
with obstructive apneas (5,18,19). The rate of water
evaporation measured from the skin was shown to
increase sharply during the development of obstructive
apneas (25,26). The increased water loss could result
from an increased sympathetic activity (5), the effort
of breathing (19) or changes in blood gases (19). The
"noisy breathing" could be equivalent to the "heavy",
"laborious", "difficult", "sonorous", "groaning",
"grunting", "loud", "stridulous", "gurgling" or "intermittently noisy" breathing reported in infants
(8,11,27), children (14,18,28-33) or adults with sleep
apnea (34). "Snoring" has been associated with airway
obstructions in infants (5) and in children (29). Because
of the sudden death of an infant with repeated snoring
and documented obstructive apnea, Guilleminault et
al. suggested that sleep studies should be performed
when snoring is reported in the absence of upper respiratory infection (11).
Although statistically related to the presence of obstructive apneas, the clinical significance of the reported symptoms should not be overestimated. Similar
signs are also found in infants with no sleep apnea
(5,17,30). Only polysomnographic monitoring can
confirm the presence of obstructive apneas, as reported
for children with clinical evidence of sleep apnea (17)
and for snoring adults (30).
It has been speculated that brief sleep apnea in infants could be related to the obstructive sleep apnea
syndrome seen in children (8,34). Hence, early diagnosis and adequate treatment of obstructed breathing
have been suggested to prevent the eventual complications seen in older children, such as failure to thrive,
repeated respiratory infections, cor pulmonale or neurologic damage (1,19,35-38). Diagnostic delays were
reported to occur because sleep apneas in infants are
frequently overlooked and because these infants may
appear normal while awake and during physical examination (1,19). Data concerning the clinical evolution of the infants studied are being collected prospectively, but are not yet available.
We conclude that in an otherwise healthy infant, a
OSA IN INFANTS
history of repeated profuse sweating and noisy breathing during sleep suggests the presence of obstructive
sleep apneas. The clinical significance of this observation is unclear and it may be premature to recommend that all such patients have polysomnography
studies. Decisions regarding further need for evaluation in these subjects should be made on a case-bycase basis.
Acknowledgements: We thank Professor H. L. Vis for his
constant encouragement. This study was supported by the
Fondation Nationale de la Recherche Scientifique (Grant
9.4524.87).
REFERENCES
I
f·
I. Brouillette RT, Fernbach SK, Hunt CEo Obstructive sleep apnea
in infants and children. J Pediatr 1982;100:31-40.
2. Cozzi F. Glossoptosis as cause of apnoeic spells in infants with
choanal atresia. Lancet 1977;iii:830-1.
3. Cozzi F, Pierro A. Glossoptosis-apnea syndrome in infancy.
Pediatrics 1985;75:836-43.
4. Kahn A, Blum D, Rebuffat E, et al. Polysomnographic studies
in infants who subsequently died of sudden infant death syndrome. Pediatrics 1988;82:721-7.
5. Kahn A, Rebuffat E, Sottiaux M, et al. Brief airway obstructions
during sleep in infants with breath-holding spells. J Pediatr 1990;
117: 188-93.
6. Kahn A, Groswasser J, Rebuffat E, et al. Sleep and cardiorespiratory characteristics of infants victims of sudden death: a prospective case-control study. Sleep 1992; 15:287-92.
7. Flores-Guevara R, Plouin P, Curzi-Dascalova L, et al. Sleep
apneas in normal neonates and infants during the first 3 months
of life. Neuropediatrics 1982; 13:21-8.
8. Guilleminault C, Souquet M, Ariagno RL. Five cases of nearmiss sudden infant death syndrome and development of obstructive sleep apnea syndrome. Pediatrics 1984;73:71-8.
9. Albani M, Bentele KHP, Budde C, et al. Infant sleep apnea
profile: preterm vs. term infants. Eur J Pediatr 1985; 143:261-8.
10. Lee D, Caces R, Kwiatkowski, et al. A developmental study on
types and frequency distribution of short apneas (3 to 15 seconds) in term and preterm infants. Pediatr Res 1987;22:344-9.
II. Guilleminault C, Ariagno RL, Forno LS, et al. Obstructive sleep
apnea and near miss for SIDS: I. Report of an infant with sudden
death. Pediatrics 1979;63:837-43.
12. Anders T, Emde R, Parmelle A. A manual of standardized terminology. technique and criteria for scoring of states of sleep and
wakefulness in newborn infants. Los Angeles: UCLA BRI Publications Office, 1971.
13. Guilleminault C, Souquet M. Sleep states and related pathology.
In: Korobkin R, Guilleminault C, eds. Advances in perinatal
neurology. New York: Spectrum Publications, 1979; I :225-47.
14. Guilleminault C, Eldridge FL, Simmons FB, et al. Sleep apnea
in eight children. Pediatrics 1976;58:23-30.
15. Krieger J. Obstructive sleep apnea: clinical manifestations and
pathophysiology. In: Thorpy MJ, Dekker M, eds. Handbook of
sleep disorders. New York: 1990:259-84.
16. Guilleminault C. Treatments of obstructive sleep apnea. In:
Guilleminault C, Partinen M, eds. Obstructive sleep apnea syndrome:clinical research and treatment. New York: Raven Press,
1990:99-118.
17. Brouillette R, Hanson D, David R, et al. A diagnostic approach
to suspected obstructive sleep apnea in children. J Pediatr 1984;
105:10-14 .
413
18. Guilleminault C. Obstructive sleep apnea syndrome in children.
In: Guilleminault C, ed. Sleep and its disorders in children. New
York: Raven Press, 1987:213-24.
19. Dyson M, Beckerman RC, Brouillette RT. Obstructive sleep
apnea syndrome. In: Beckerman RC, Brouillette RT, Hunt CE,
eds. Respiratory control disorders in infants and children. Baltimore: Williams and Wilkins, 1992:212-30.
20. Diagnostic Classification Steering Committee, Thorpy MJ,
Chairman. International classification of sleep disorders: diagnostic and coding manual. Rochester: American Sleep Disorders
Association, 1990.
21. Gunn TR, Tonkin SL. Upper airway measurements during inspiration and expiration in infants. Pediatrics 1989;84:73-7.
22 .. Abu-Osba YK, Mathew OP, Thach BT. An animal model for
airway sensory deprivation producing obstructive apnea with
postmortem findings of sudden infant death syndrome. Pediatrics 1981 ;68:796-801.
23. Thach BT. Neuromuscular control of the upper airway. In:
Beckerman RC, Brouillette RT, Hunt CE, eds. Respiratory control disorders in infants mid children. Baltimore: Williams and
Wilkins, 1992:47-60.
24. Stein schneider A, Weinstein SL, Diamond D. The sudden infant
death syndrome and apnea/obstruction during neonatal sleep
and feeding. Pediatrics 1982;70:858-63.
25. Kahn A, vanden Merckt C, Dramaix M, et al. Transepidermal
water loss during sleep in infants at risk for sudden death. Pediatrics 1987;80:245-50.
26. Kahn A, Rebuffat E, Sottiaux M, et al. Briefairway obstructions
during sleep in infants with breath-holding spells. Reply. J Pediatr 1991; 118:825-6.
27. Tonkin S. Sudden infant death syndrome: hypothesis of causation. Pediatrics 1975;55:650-6.
28. Guilleminault C, Korobkin R, Winkle R, et al. A review of 50
children with obstructive sleep apnea syndrome. Lung 1981',59:
275-87.
29. Felman AH, Loughlin GM, Leftridge CA, et al. Upper airway
obstruction during sleep in children. AJR 1979;133:213-16.
30. Hillerdal G, Hetta J, Lindholm CE, et aJ. Syptoms in heavy
snorers with and without obstructive sleep apnea. Acta Otolaryngol (Stockh) 1991;111 :574-81.
31. Frank Y, Kravath RE, Pollak CPo Obstructive sleep apnea and
its therapy: clinical and polysomnographic manifestations. Pediatrics 1983;71 :737-42.
32. Weissbluth M, Davis AT, Poncher J, et al. Signs of airway
obstruction during sleep and behavioral, developmental and
academic problems. J Dev Behav Pediatr 1983;4: 119-28.
33. Sullivan CE, Grunstein RR, Marrone 0, et al. Sleep apneapathophysiology: upper airway and control of breathing. In:
Guilleminault C, Partinnen M, eds. Obstructive sleep apnea syndrome: clinical research and treatment. New York: Raven Press,
1990:49-69.
34. Guilleminault C, Heldt G, Powell N, Riley R. Small upper airway in near-miss sudden infant death syndrome infants and
their families. Lancet 1986;i:402-7.
35. Mark JD, Brooks JG. Sleep-associated airway problems in children. Pediatr Clin North Am 1984;31:907-18.
36. Luke MJ, Mehrizi A, Folger GM, et al. Chronic nasopharyngeal
obstruction as a cause of cardiomegaly, cor pulmonale, and
pulmonary edema. Pediatrics 1966;37:762-8.
37. Menashe VD, Farrehi C, Miller M. Hypoventilation and cor
pulmonale due to chronic upper airway obstruction. J Pediatr
1965;67: 189-203.
38. Ross RD, Daniels SR, Loggie JMH, et al. Sleep apnea-associated
hypertension and reversible left ventricular hypertrophy. J Pediatr 1987; III :253-5.
.
'
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