Larry Consenstein, MD
Mednax Medical Group
Syracuse, NY
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History of monitoring
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Apnea of prematurity
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Description
Significance
Treatment
Intermittent hypoxia
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SIDS and SIDS risks
Frequency
Morbidity
Unapparent
ALTE
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Workup
Epidemiology
Follow up
Peds Jan 2016
Peds Jan 2016
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Cessation of breathing in premature infants
Definitions vary but most widely used
definition states apnea of prematurity is
cessation of breathing lasting > 15-20
seconds, or less if associated with cyanosis,
abrupt pallor, hypotonia or bradycardia
The apnea may be central (10-25%),
obstructive (10-25%) or mixed (50-75%)
GER is not causally associated with these
events, and treatment does not reduce
alarms.
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Respiratory support:
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Flow cannula, HFNC delivering CPAP, CPAP,
ventilation
Mechanisms- dilate upper airway, non-specific
airway stimulation, improved pulmonary function
Medications:
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Primarily caffeine
Mechanism- increased sensitivity of brainstem
chemoreceptors to CO2
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Caffeine for Apnea of Prematurity Trial (NEJM
2006;354:2112)
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Open label, placebo controlled, multi-center trial of 963
babies 500-1250 g.
Evaluated use of oxygen, ventilation, CPAP, weight gain.
Babies in study group used less respiratory support, less
steroids, had fewer transfusions, and a lower risk of BPD,
and lower incidence of PDA, without significant short
term complications.
Overall, they also had improved neurologically intact
survival at 18-21 months
Mechanism of benefit not identified
JAMA Pediatr 2014
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Apnea >5 sec. w/o bradycardia, desaturation,
did not result in decrease CBF in healthy term
infants (Rehan, 1995)
Watkin (1996) measured O2 saturations after
pauses of nasal airflow of >4 sec. 72% of
apneas were associated with a decrease of >3%
saturation
18/30 preterm infants studied at 33 wks had
saturations fall to <80% 161 times; 97% were
associated with central or obstructive apneas or
pauses (Adams, 1997)
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At 32 weeks PCA, 60% of apneas have
bradycardia, and 86% of bradycardias are
associated with apnea (Upton,1991)
At 36 weeks PCA 58% of infants studied at
discharge had bradycardias. 83% were
associated with apnea, 86% with desaturations
(Poets, 1993).
In an earlier study, most episodes of
bradycardia (<100 bpm) were associated with a
decrease in saturation to <80% (Poets, 1991)
Oxygen desaturation frequently accompanies
apnea, and varies with the length of apnea
(Carbone, 1999)
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Barrington (1996) studied 187 infants at
discharge, and 91% had significant apnea (>12
sec.), associated with mean decrease in
saturation of 13%
Graf (1991) showed 4/9 infants with significant
abnormalities on 4 channel recordings had
normal 2 channel recordings; all had events
after discharge
Apnea frequently persists beyond term in
infants born at 24-28 weeks (Eichenwald, 1997)
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In the NICU, babies had bedside monitor
results recorded and compared with nurse
observations (Am J Perinatol 2013;30:643).
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7.7% of nurse recorded apneas were confirmed by
recording
Of true apneas, 99% were confirmed by bedside
monitors, but only 7.6% were recorded by nurses.
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Compared France, Canada and US
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Pre-discharge recordings:
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Canada 65%, France 68%, US 99%
Home caffeine:
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Canada 100%, France 96%, US 92%
Discharge on monitor:
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Canada 45%, France 38%, US 24%
Apnea free days required:
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Academic units surveyed
Response rates 79-89%
Canada 40%, France 34%, US 64%
Discharge at > 40 weeks:
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Canada 60%, France 60%, US 33%
J Neo Perinatal
Med. 2015, 8,
p307
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The biphasic ventilatory response persists into
the second postnatal life in preterm infants
(Martin, 1998)
Exposure to hypoxia in developing animals may
have lasting effectsRats exposed to a single episode of anoxia on day 3
have altered hypoxic ventilatory response when
evaluated at 25 days (Saiki, 1999)
 Episodic exposure to hypoxia at 3 days can enhance
late hypoxic ventilatory response later in life, possibly
secondary to enhanced NO production (Gozal, 1999)
 The Hering-Breuer reflex is enhanced in 2 wk animals
exposed to repeated hypoxic exposures on d3
(Matsuoka, 1999)
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Some genes may be activated by hypoxia:
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Induce an upregulation of erythropoesis via
hypoxia-inducible factor 1
Affect vascular function
Affect cell metabolism, particularly glycolysis
(Waddell,1999)
Affect genes responsible for progammed cell
death (Mishra, 1999)
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Patients with BPD may have altered
respiratory control:
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When infants with BPD were studied with
alternating breaths of mild hypoxia, they did not
demonstrate the increase in ventilation seen in the
controls, indicating an impaired chemoreflex
(Calder, 1994)
Exposure to hyperoxia should result in a fall in
minute ventilation. This chemoreflex does not occur
in infants with BPD (Katz-Salamon, 1995)
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More ROP is seen with more intermittent
hypoxia (Di Fiore, et al, J Pediatr, 2010)
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May be more than seen with hyperoxia episodes.
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788 citations screened
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55 met criteria for inclusion in review.
78.2% reported an adverse effect.
All ages except premature newborns.
Decreased IQ seen with sleep disordered
breathing.
Effects also seen on behavior and development.
Patient populations included SDB, congenital
heart disease and chronic respiratory disorders.
Pediatr 2004
Intermittent
hypoxia in
OSA
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In preterm babies:
Devel Sci 2006
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Babies with BPD
Devel Sci 2006
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Collaborative Home Infant Monitoring
Evaluation (CHIME) (Hunt, et al, J Pediatr 2004)
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Randomized home monitoring study
Developmental follow done and compared with
number of documented alarms
Monitored for 3-4 months
Both term and preterm infants with 5+ events
(apnea, bradycardia, oxygen desaturations) had
significantly lower MDI
Events associated with median drop of SaO2 of 2030%
Devel Sci 2006
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An apparent life-threatening event (ALTE) was
defined at a consensus development conference
convened in 1986 by the National Institutes of
Health to address the relationship between sudden
infant death syndrome
An ALTE was defined as “an episode that is
frightening to the observer and that is
characterized by some combination of apnea
(central or occasionally obstructive), color change
(usually cyanotic or pallid but occasionally
erythematous or plethoric), marked change in
muscle tone (usually marked limpness), choking,
or gagging.”
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Epidemiology
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Age < 30 days, gestational age <30 weeks associated
with recurrent events.
ALTEs may be more frequent in babies with GERD.
 However, GERD not more likely in first ALTE.
 Many studies have shown no relationship between
reflux and apnea (though apnea may cause reflux).
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If multiple events, more likely to have underlying
cause.
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Etiology
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Suspected child abuse (including Munchausen by
proxy). Consider other signs (signs of trauma,
retinal hemorrhages, sudden hypotonia, etc.).
Suspected seizures
Viral illness. Rare in the absence of other respiratory
signs.
Neurologic. Imaging likely positive with signs of
abuse. Overall, low yield for imaging in the absence
of other signs.
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Possible etiologies:
Anemia. No evidence.
 Bacterial infection. Rarely can be pertussis, no
evidence of meningitis, rarely UTI.
 No evidence for toxic ingestions.
 Metabolic disorders possible if associated signs, or if
recurrent.
 No evidence for cardiac arrythmias by routine
Holter screening.
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Work-up (in most hospitals):
CBC (70%)
 BMP (65%)
 CXR (69%)
 UGI or swallow (26%)
 EKG (36%)
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Subsequent apnea
and/or bradycardia
is rare in babies with
ALTE who were
discharged on home
monitors.
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Defined as apnea >30 sec, bradycardia >10 sec,
and desaturation >10 sec <80% (J Pediatr
2009;154:332)
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Relative risks
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Diagnoses (46 of 625 ALTE admissions):
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Viral URI, 30
Pertussis, 2
Metabolic disorder, 1
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Questions?
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Poets (1993) showed children 2-16 y.o may
have pauses of 20 sec. or longer and
desaturations to less than 90% (47% of children
2-6 y.o.)
Hunt (1996) followed 88 term infants <19 wk
old, showed 10% had saturations less than 90%,
of varying length, no bradycardia, and rare
apnea over 20 sec.