Apnea of Prematurity: Current Practices and

Future Directions
Kalpashri Kesavan, MBBS,* Joanna Parga, MD*
*Division of Neonatology and Developmental Biology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA

Education Gap
Definitions and treatment strategies for apnea of prematurity vary widely in
clinical practice and clinicians are in need of a consensus.

Abstract
Apnea of prematurity (AOP) is a developmental disorder affecting most
infants born at less than 34 weeks’ gestational age. AOP is one of the most
common diagnoses in the NICU, contributing substantially to prolonged
hospitalization. Despite its frequent occurrence in premature neonates born
at less than 37 weeks’ gestation, there is no common consensus on its
definition, monitoring practices, and clinical relevance, leading to significant
variation in practice. It is also not clear how and if repeated apneas,
bradycardias, and hypoxemia are indeed detrimental to the developing
neonate. This article reviews the definitions of AOP and the current standard
of care for AOP, which includes positioning, positive pressure ventilation, and
methylxanthine therapy. We also explore some novel therapies, as well as
address controversies in initiating treatment, length of treatment, and
guidelines for discharge.

Objectives After completing this article, readers should be able to:

AUTHOR DISCLOSURE Drs Kesavan and 1. Review the definition of apnea of prematurity.
Parga have disclosed no financial
relationships relevant to this article. This 2. Review the epidemiology of this developmental disorder.
commentary does not contain a discussion of
an unapproved/investigative use of a 3. Explore various treatment options for apnea of prematurity.
commercial product/device.
4. Address the contribution of gastroesophageal reflux to apnea of
ABBREVIATIONS prematurity.
AOP apnea of prematurity
GER gastroesophageal reflux 5. Discuss treatment and discharge planning in infants with apnea of
CNS central nervous system prematurity.
CO2 carbon dioxide
CPAP continuous positive airway pressure
NIPPV nasal intermittent positive pressure
ventilation
SpO2 oxygen saturation
PMA postmenstrual age

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 INTRODUCTION
Each year 15 million infants are born premature (<37 weeks’
gestation) worldwide, and that number is on the rise. (1) In the
United States, approximately 9.6% of infants are born pre-
term. (2) Apnea of prematurity (AOP) is a developmental
condition affecting essentially all preterm infants born at less
than or equal to 28 weeks’ gestation and lower proportions
as one approaches term. Even at 34 weeks’ gestation, 20%
of infants have AOP. (3) The term AOP includes episodes of
apnea or breathing pauses, bradycardia, and intermittent
hypoxemia either solely or in combination. AOP may last
up to 44 weeks’ postmenstrual age (PMA). (4)(5) One of the
main concerns with breathing pauses or apnea is the accom-
panying intermittent hypoxia, the sequential and repetitive
exposure to low oxygen, followed by a rapid increase in oxygen.
(6) Ventilatory and perfusion disturbances from such breath-
ing patterns are potentially associated with sequelae such as
retinopathy of prematurity, altered growth and cardiovascular
regulation, and neurodevelopmental disabilities. (7) Therapies
for AOP may include prone positioning, continuous positive
airway pressure (CPAP), or nasal intermittent positive pres-
sure ventilation (NIPPV) to prevent pharyngeal collapse and
alveolar atelectasis. The cornerstone of AOP treatment is
methylxanthines (caffeine, theophylline) to block adenosine
receptors. (8)(9)(10) In addition, affected infants require con-
tinuous vital sign monitoring. In general, complete cessation
of those events is required for a period before discharge. This
creates a challenge for practitioners. There is no consensus on
the definitions and causes of significant AOP. (11) This article
attempts to address controversies and provide clinicians with
guidelines for the management of AOP.
DEFINING AOP
Apnea is defined as a temporary cessation of breathing or
airflow for more than 20 seconds. Apnea frequently occurs
in preterm infants. However, defining clinically significant
apnea in infants of less than 37 weeks’ gestation is frequently
debated among clinicians. Most definitions consider apnea
as cessation of breathing lasting 15 to 20 seconds. Apnea that
lasts for less than 10 seconds is considered “significant” if it
is associated with a decrease in oxygen saturation (SpO2) to
less than or equal to 80% or 85%, whereas “significant”
bradycardia has been defined as a decrease in heart rate to less
than 80 beats/min or less than two-thirds of baseline. (12)
However, it should be noted that there is no single definition
within the medical community for AOP. Other etiologic
factors for the clinical findings should be considered before
assigning the diagnosis of AOP.
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MECHANISMS AND PATHOPHYSIOLOGY OF AOP
AOP results from developmental immaturity of several me-
chanisms involved in regulating respiratory control and in
maintaining patency of the upper airway. The causes of apnea
can be divided into 3 major groups based on the mechanism:
1) central, 2) obstructive, or 3) mixed (a combination of central
and obstructive).
1. Central apnea is related to immaturity of the central
nervous system (CNS), with preterm infants exhibiting
fewer neuronal connections, poor myelination of the
brain stem, and immature chemoreceptor function
and response. (13) In central apnea, there is no evi-
dence of obstruction to airflow, but there is absence of
chest wall motion. Central apnea results from:
a) Enhanced sensitivity to neurotransmitters. Premature
infants have enhanced sensitivity of the respira-
tory control system to inhibitory neurotransmitters
(ie, g-aminobutyric acid, adenosine, serotonin, and
prostaglandin) that can lead to apnea. (14)(15)
b) Hypoxic ventilatory depression. Repeated exposure to
episodes of hypoxia, such as might occur in an infant
with chronic lung disease, can increase peripheral
chemoreceptor sensitivity in the carotid body, and
result in an apneic response to a brief episode of
hyperoxia. In other words, preterm infants mani-
festing hypoxia more often tend to compensate for
higher oxygen levels (normal or hyperoxia) with apnea.
(14)(15)(16)
c) Impaired hypercapnic ventilatory response. The ven-
tilatory response to carbon dioxide (CO2) is mainly
mediated by central chemoreceptors in the medulla.
Preterm infants have a blunted or absent respiratory
response to hypercapnea. These children prolong expi-
ratory time (but do not increase respiratory rate or tidal
volume), which may lead to less minute volume and
uncoordinated movements of respiratory muscles in
response to hypercapnea, leading to apnea. In addi-
tion, both term and preterm infants have a CO2
apneic threshold (CO2 level below which apnea is
triggered) that is only slightly below the normal baseline
partial pressure of CO2. As a result, even brief periods
of hyperventilation might trigger apneic episodes.
(14)(15)
d) Laryngeal chemoreflex. Activation of laryngeal chemo-
receptors (via superior laryngeal nerve afferents) can
result in apnea, bradycardia, and hypotension. This
phenomenon is known as the laryngeal chemoreflex. It
is a sensory mechanism to defend against aspiration of
liquids. It is exaggerated in preterm infants and may, in
 some infants, be responsible for the apnea seen in DIAGNOSING AOP
association with feeding or reflux episodes.
To detect events associated with AOP, clinicians rely on
e) Sleep state. Neonates spend most of their time in
standard NICU monitoring systems that gather continuous
active sleep. Apneas are more common during active
vital sign data as well as nursing reports. (3) Heart rate is
sleep when respirations are irregular. Changes in
identified through electrocardiographic signaling, and car-
neuromodulatory inputs and generalized inhibition
diac alarms are activated if the heart rate drops below a
of skeletal muscle activity during sleep are also
set point, generally 100 beats/min. This may vary among
contributory.
NICUs. Respiratory rate is largely captured with impedance
2. Obstructive apnea in preterm neonates presents clini-
probes that monitor chest wall movement. These probes are
cally with the preservation of chest wall movement.
notoriously unreliable, and without the use of capnography,
However, airflow is extinguished secondary to lack of
frequently miss episodes of obstructive apnea. (3) Pulse
coordination of respiratory musculature, pharyngeal
oximetry (comparing the absorption of red and infrared
instability, neck flexion, or nasal obstruction. (13) The
light by hemoglobin) is used to determine SpO2. Variation of
pharynx is the most collapsible portion of the upper
usage of the aforementioned monitors, as well as an under-
airway, and central regulation of pharyngeal tone is
estimation or misinterpretation of clinical findings by bed-
important for maintaining airway patency. Premature
side nursing, will influence which events are considered
infants at baseline have less rigid airways.
significant and when an infant may be discharged from the
3. Mixed apnea has components of both obstructive and
hospital. (18)
central apnea. In most premature neonates, the sequence
typically observed is an initial loss of central respi-
ratory drive, followed by recovery and delayed acti-
CONSEQUENCES OF AOP
vation of upper airway muscles superimposed on a
closed upper airway, leading to prolonged mixed apnea AOP is considered a developmental disorder that resolves
episodes. (17) with increasing maturity and gestational age. The hypox-
A summary of causes and pathophysiology of apnea in emia and perfusion changes accompanying apnea could
preterm neonates is provided in Table 1. damage vital organs and tissues. The effects of recurrent

TABLE 1. Etiology and Pathophysiology of Apnea in Premature Neonates

CENTRAL APNEA OBSTRUCTIVE APNEA OTHER CAUSES OF APNEA

Peripheral chemoreceptors (carotid body):
Used to a lower PaO2 in utero (w30),
increases
4 after delivery, silences
peripheral chemoreceptors
Laryngeal chemoreflex: Exaggerated reflex,
vagal stimulation, may be associated with
GERD but controversial, likely associated
with delayed gastric emptying
Inhibitory neurotransmitters:
Exaggerated responses to
GABA, adenosine, serotonin,
and prostaglandin
Sleep state: Predominance of REM sleep,
increased paradoxical breathing
Chest wall: Lacks stability, highly compliant,
contradictory movements in response to
hypercapnia
Pharyngeal obstruction: Pharynx is the most
collapsible portion of the upper airway
Tracheomalacia and larynogomalacia
Neck flexion: Interference with patency of
pharyngeal muscles
Nasal obstruction: From swelling
or NG tubing
Genetic predisposition: Congenital central
hypoventilation syndrome, craniofacial
anomalies, trisomy 21, Prader-Willi
syndrome
CNS disturbances: Seizures, intraventricular
hemorrhage, hypoxic-ischemic
encephalopathy, neuromuscular disorders,
medications (sedative analgesics,
anticonvulsive)
Infection/sepsis: Respiratory tract infections,
urinary tract infections, meningitis,
necrotizing enterocolitis
Cardiovascular: Arrhythmias,
cardiomyopathies, patent ductus arteriosus,
congenital heart disease
Hematologic: Anemia, polycythemia
Metabolic disturbances: Hypoglycemia,
electrolyte imbalances, inborn errors of
metabolism

CNS¼central nervous system; GABA¼g-aminobutyric acid; GERD¼gastroesophageal reflux disease; NG¼nasogastric; PaO2¼partial pressure of oxygen;
REM¼rapid eye movement.

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 fluctuations in breathing, heart rate, and SpO2 on premature
infants’ growth and neurodevelopment are not well defined.
Intermittent hypoxemia has the potential to activate proin-
flammatory cytokines and cascades, creating disturbances in
growth, bone metabolism, retinal development, cardiorespi-
ratory instability, and neurodevelopment (reviewed by Martin
et al [7]) (Fig 1). Studies examining whether adverse neuro-
developmental outcomes might be related to AOP struggle
with the inability to accurately define the severity and fre-
quency of apneic events using nursing and vital sign mon-
itor outputs. There is no direct evidence supporting such a
relationship. Nonetheless, some retrospective investigations
suggest that increasing severity and duration of apnea during
the neonatal period could be associated with worse neuro-
developmental outcomes. (19)(20)(21) Unfortunately, each of
these publications has major methodologic problems. There
are no neuroimaging or electroencephalographic findings
that are specifically associated with AOP. A major difficulty
is ascertaining whether neurodevelopmental sequelae are
due to the events of AOP or whether an already abnormal
brain in a premature infant predisposes the child to have
more events (the old “which came first, the chicken or the
egg” argument). Clearly, prospective investigations are war-
ranted to further define connections between AOP and
outcomes. Importantly, it needs to be established whether
various therapies for AOP may mitigate any potential adverse
outcomes.
TREATMENT AND INTERVENTIONS FOR AOP
Without clear evidence of the extent of morbidity that arises
from AOP, clinicians treat under the assumption of pre-
sumed harm without intervention. Treatments for AOP are
relatively limited and may have side effects. As such, some
advocate for the development of apnea severity scores to
improve and inform treatment decisions. (22) All preterm
infants born at less than 35 weeks’ gestational age should
have cardiorespiratory monitoring for apnea, bradycardia, and
Figure 1. Evidence from animal and human studies showing the pathologic consequences of apnea and intermittent hypoxia (IH).
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desaturation events in a NICU. There is a lack of consensus on
what constitutes a significant cardiorespiratory event. How-
ever, most practitioners consider the following parameters as
being significant and requiring continued observation and/or
treatment:
1. Apnea for more than or equal to 15 to 20 seconds
2. A shorter breathing pause that is associated with bra-
dycardia of less than or equal to 80 to 100 beats/min and/
or oxygen desaturation to less than or equal to 80% to
85%.
Interventions for AOP include pharmacologic, positional,
and ventilator techniques. A guideline for AOP management
is provided here and a detailed description of treatments is
discussed (Fig 2). Treatment should be considered when
apneic events are frequent and/or prolonged, when they
are associated with bradycardia (£100 beats/min), or oxygen
desaturations (£80%–85%), or if the events require interven-
tion, that is, frequent tactile stimulation or bag and mask
ventilation.
Preventive Measures
a) Position. Avoid extreme flexion or extension of neck to
maintain patency of upper airway. Consider prone posi-
tioning. (23)
b) Ambient temperature. Provide a stable thermal environ-
ment as temperature fluctuations can precipitate apneic
episodes. (24)
c) Nasal patency. Limit nasal suctioning, use heated humid-
ified air to prevent crusting of nasal secretions, and use
appropriately sized nasal cannulas.
d) Maintain SpO2. Supplemental oxygen should be provided
as needed to avoid hypoxia and maintain SpO2 between
88% and 94%, because hypoxia can lead to severe desat-
uration episodes.
Pharmacologic Intervention
The most common pharmacologic intervention is methyl-
xanthine therapy, that is, theophylline or caffeine citrate
Figure 2. Management strategies for infants with symptomatic apnea of prematurity. Intervention stratified by perceived severity of events. (Adapted
from Di Fiore et al [22].) BW¼body weight; FiO2¼fraction of inspired oxygen; SpO2¼oxygen saturation.

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 (Table 2). Theophylline was traditionally used before 1995,
but has now been largely replaced by caffeine citrate because
of the latter’s once-a-day dosing, longer half-life, broader
therapeutic range, good safety profile, and elimination of
close monitoring of blood levels. (13) Adenosine is an
inhibitory neurotransmitter in the CNS, and the main mech-
anism of methylxanthine action is the antagonism of aden-
osine receptors in the CNS. Methylxanthines improve the
respiratory drive, increase minute ventilation and CO2 sen-
sitivity, decrease hypoxic ventilator depression, and improve
diaphragmatic contractility. (13) These drugs also have weak
diuretic action and may improve lung compliance, especially
in the setting of chronic lung disease. (25) In general, caffeine
is recommended for all infants born at less than or equal to
28 weeks’ gestation. Some recommend treating all infants
between 29 and 32 weeks, because most of these infants will
have events. Beyond 32 weeks, clinical practices vary with
regard to caffeine boluses and the initiation of maintenance
therapy. Such an approach should be considered in infants
of less than or equal to 34 weeks’ gestation when there are
symptoms of AOP. (9)(26)(27)
A large randomized controlled trial has demonstrated that
caffeine therapy significantly reduces the rate of bron-
chopulmonary dysplasia, as well as the need for medical
or surgical closure of patent ductus arteriosus. (28) Although
initial follow-up studies at 18 to 21 months of age revealed
improved neurodevelopmental outcomes in caffeine-treated
children, (29) there were no differences when the children
were followed to 5 years of age. (30) In addition, caffeine
therapy may have side effects. Tachycardia, cardiac dysrhyth-
mias, seizures, feeding intolerance, and increased metabolic
demand, leading to diminished growth in preterm infants
have been observed. (13) Treated infants should be monitored
closely for the development of any of these side effects,
especially when considering dosage increases. Although
serum concentration of caffeine is not routinely obtained
because of the wide therapeutic range of 5 to 25 mg/L, it is
important to note that the therapeutic range can be frequently
exceeded even at standard caffeine doses (Table 2) due to fluid
TABLE 2. Medications for Treatment of Apnea of Prematurity
MEDICATION ROUTE DOSE
Caffeine IV/PO Load: 20 mg/kg then
citrate 5-10 mg/kg/day maintenance therapy
Theophylline PO Load: 5-6 mg/kg then 2-6 mg/kg/day
maintenance therapy
IV¼intravenous; PO¼enteral.
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imbalances and illnesses that alter metabolism, distribution,
and excretion of caffeine in a premature neonate. (31)(32)
There are no clear guidelines for when to discontinue
caffeine. Most clinicians discontinue caffeine around 33
to 34 weeks’ PMA or if the infant has been apnea free for
more than or equal to 7 days. It is generally acceptable to
discontinue caffeine between 32 and 34 weeks’ PMA if there
have been no apneic events requiring intervention over the
previous 5 to 7 days. (33) Recent evidence suggests that
prolonged caffeine therapy beyond 34 weeks’ PMA may
decrease intermittent hypoxic events. (34) However, the
immediate clinical significance of these events and their
long-term effects are lacking, necessitating more rigorous
studies to address these concerns.
Another pharmacologic intervention explored for AOP
is doxapram. (13)(22) Doxapram is thought to stimulate
peripheral chemoreceptors at low doses and central che-
moreceptors at higher doses. However, a concern for adverse
effects such as irritability, hypertension, and decreased cere-
bral blood flow has limited its use. Other less-studied inter-
ventions include increasing inspired CO2 concentrations,
using oxygen, and providing red blood cell transfusions
(22); however, all require more studies.
Respiratory Strategies
A well-studied proven intervention targets the dynamic upper
airway obstruction that results in apneic episodes. Adminis-
tering positive pressure to splint airways open using non-
invasive respiratory support decreases atelectasis, improves
oxygenation, reduces apneic events, and significantly improves
extubation success. (22) To achieve this, nasal CPAP, validated
synchronized NIPPV, and nasal cannula (high or low flow)
are options for treatment. CPAP improves oxygenation by
improving ventilation-perfusion mismatch and optimizes
the functional residual capacity; also it improves ventila-
tion by decreasing respiratory rate, and prolongs expiratory
time without affecting the ventilator response to CO2. (35)
(36) High-flow nasal cannulas also operate in a similar
fashion by delivering CPAP; however, the levels of positive
FREQUENCY MONITORING
Every 24 h Heart rate, apnea, serum caffeine levels if
appropriate
Divided Respiratory rate, heart rate, apnea, serum
Every 8–12 h theophylline levels
pressure they generate are unpredictable. NIPPV is an
enhanced version of CPAP that delivers intermittent lung
inflations set to a peak pressure delivered through nasal
prongs or mask. (37)
Treating Gastroesophageal Reflux
In some units, gastroesophageal reflux (GER) is treated
because of the belief that GER precipitates episodes of
apnea. The mechanism could be secondary to the laryngeal
chemoreflex. However, studies do not definitively identify
a link between reflux and apnea. (3)(14)(15)(38) Pharma-
cotherapy for GER has not been shown to be of benefit in
preventing AOP. (39) Moreover, such therapy may have
adverse effects, such as an increased incidence of necro-
tizing enterocolitis due to alterations of microbial flora
from acid suppression. These therapies do not address the
underlying etiology of poorly developed musculature in the
preterm infant. (3)
Upcoming Therapies for AOP
It is common for interventions for AOP to attempt to
address symptoms, but not aid CNS maturation. However,
there are several interventions that have the potential to
elucidate ways to noninvasively bolster native CNS activity
in the prevention of apnea. These interventions include
olfactory stimulation, (40) mechanosensory stimulation,
(41)(42) and sound stimulation in the form of music. (43)
Each has the potential to influence cranial nerves and work
to stimulate and mature them. Large, prospective, random-
ized, controlled trials are needed to appropriately evaluate
these therapies.
A summary of interventions for AOP is provided in Table 3.
TABLE 3. Interventions for Apnea of Prematurity
PREVENTIVE PHARMACOLOGIC
MEASURES INTERVENTIONS
Positioning: Consider Methylxanthine therapy
prone (caffeine citrate)
Thermoneutral Doxapram
environment
Maintain nasal patency
Maintain SpO2 between
88%–94%
CO2¼carbon dioxide; GER¼gastroesophageal reflux; SpO2¼oxygen saturation.
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DISCHARGE CONSIDERATIONS
There are no definitive criteria for discharge of premature
infants who have manifested episodes of apnea, oxygen
desaturation, and bradycardia. In a survey in which 252
neonatologists responded, 75% recommended a 5- to 7-day
period of observation free of episodes related to AOP before
discharge. (33) After this event-free period, the risk for
subsequent occurrence of a clinically significant cardiore-
spiratory event is very low. (44) Other surveys reveal sub-
stantially different opinions concerning discharge criteria.
(18) Much of this variation comes from lack of a standard-
ized approach to monitored events and differences in clin-
ical interpretation of these events. (18)(33) Although recent
data suggest that standard bedside monitors are far more
reliable than nurse-recorded cardiorespiratory events, (45)
clinical interpretation is relied upon more heavily than the
monitors. (33) Many experts do not “count” feeding-relating
episodes in determining when to discharge these infants. (3)
Given that preterm infants are surviving at higher rates
and the landscape of health-care delivery in the United
States is changing, there is increased focus on resource
constraints and decreasing hospitalization times for these
infants. (46)(47) However, because of the considerable var-
iation in practice, no concrete discharge-planning guide-
lines have been recommended at this time. The prognostic
significance of persistent mild bradycardia, desaturation
events, and short respiratory pauses that are detected by
cardiorespiratory monitors is unclear; optimal decision
making in terms of discharge from the hospital for a pre-
term infant, now past term and ready for discharge, remains
an issue at large. (3) The most successful early discharge
program will cite apneic episodes and feeding difficulties as
VENTILATORY STRATEGIES OTHERS
Continuous positive airway pressure Noninvasive stimulation: Olfactory,
mechanosensory, sound
High-flow nasal cannula Increased inspiratory CO2
concentration
Synchronized nasal intermittent Oxygen administration
positive pressure ventilation
Red blood cell transfusions
Management of GER
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 barriers to discharge and promote the development of
community-based programs with individualized support
and education for families as a potential cost-effective and
discharge-friendly model. (48) However, few hospitals have
the resources to provide these community-level interven-
tions and further research is needed to standardize clini-
cians’ definitions of significant apnea to help guide the safe
discharge of preterm infants. (49)
AOP AND SUDDEN INFANT DEATH SYNDROME
Infants born preterm with a history of AOP in the neonatal
period were noted to have higher baseline heart rates and lower
heart rate variability in the first several months after birth,
suggesting an alteration in the autonomic function, (50) similar
to findings in infants who had died of sudden infant death
syndrome (SIDS). (51)(52) However, there is no direct evidence of
a causal relationship between AOP and SIDS. (53)(54) Episodes
of AOP do not predict the recurrence of clinically significant
postdischarge events, SIDS, or the need for hospital readmission.
(3) In the setting of intrauser variation in the interpretation of
cardiorespiratory monitoring, home monitoring to decrease
the incidence of SIDS is not recommended and has not been
proven to reduce the risk of SIDS. (55) In addition, AOP is gen-
erally seen to resolve around 44 weeks’ PMA, and in extremely
premature infants, SIDS typically occurs at approximately 47
weeks’ PMA; thus AOP and SIDS are not considered to be
related. (3) Nonetheless, the autonomic immaturity and dys-
function seen in premature infants who have had persistent
AOP could explain the increased risk of SIDS (56) in prema-
ture infants, and thus is an important consideration for both
the clinician and families caring for former preterm infants.
American Board of Pediatrics
Neonatal-Perinatal Content
Specifications
• Know the pathophysiology of apnea of prematurity.
• Know the management of apnea of prematurity.
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NeoReviews Quiz
There are two ways to access the journal CME quizzes:
1. Individual CME quizzes are available via a handy blue CME link in the Table of Contents of any issue.
2. To access all CME articles, click “Journal CME” from Gateway’s orange main menu or go directly to: http://www.
aappublications.org/content/journal-cme.

1. A female infant born at 28 weeks’ gestational age is now 4 weeks old. She required NOTE: Learners can take
continuous positive airway pressure during the first 2 weeks, but now is in room air. She is NeoReviews quizzes and
noted on continuous monitoring to have episodes of apnea and bradycardia. Which of the claim credit online only
following statements regarding apnea of prematurity is correct? at: http://Neoreviews.org.
A. At this infant’s age, accounting for the gestational age at birth, apnea of pre-
maturity would not be considered as part of the differential diagnosis for this To successfully complete
infant’s symptoms. 2017 NeoReviews articles
B. Preterm infants have enhanced sensitivity of the respiratory control system to for AMA PRA Category 1
inhibitory neurotransmitters, such as serotonin, that can lead to apnea. CreditTM, learners must
C. Preterm infants have abnormally insensitive laryngeal chemoreceptors, leading to demonstrate a minimum
chronic aspiration and hypoxia, leading to oxygen desaturation, followed by performance level of 60%
bradycardia and then apnea. or higher on this
D. Central apnea in preterm infants presents with preservation of chest wall assessment, which
movement. measures achievement of
E. Preterm infants at baseline have extremely rigid airways, leading to increased the educational purpose
turbulence and decreased compliance, which causes hypoxia and resulting apnea. and/or objectives of this
2. A female infant born at 28 weeks’ gestational age is 3 weeks old and having occasional activity. If you score less
apnea and bradycardia events, with SpO2 decreasing during events to the 70% to 80% than 60% on the
range. She is in room air and receiving full enteral feedings. Which of the following steps assessment, you will be
may help in management of this patient? given additional
A. Avoiding extreme flexion or extension of the neck and considering prone opportunities to answer
positioning. questions until an overall
B. Providing slightly lower thermal environment to keep infant temperature mildly 60% or greater score is
hypothermic at 35.5 to 36.0°C. achieved.
C. Deep nasal suctioning every 3 hours just before feedings.
D. Oxygen hood to provide 100% inspired oxygen. This journal-based CME
E. Discontinuing continuous monitoring to limit interventions and check SpO2 only activity is available
once per 12-hour shift. through Dec. 31, 2019,
3. An infant born at 26 weeks’ gestational age is now 2 days old and receiving mechanical however, credit will be
ventilation. He is ready to be extubated because of low inspired oxygen and pressures. You recorded in the year in
are considering the next steps in clinical management. Which of the following statements which the learner
describes appropriate next steps for this patient? completes the quiz.
A. If the patient is not currently having any episodes of apnea, caffeine therapy should
be avoided or delayed until events occur.
B. The infant should initially be started on theophylline and then transitioned to
caffeine at 3 weeks of age.
C. A randomized controlled trial has shown that caffeine therapy can reduce the risk
of bronchopulmonary dysplasia.
D. There is no evidence that providing positive pressure at this stage in the form of
continuous positive airway pressure will have any benefit compared to no
respiratory support.
E. The patient should be started on antireflux medication to reduce airway
inflammation.
4. A 26-week gestational age infant is receiving mechanical ventilation for the first day after
birth and then continuous positive airway pressure for 1 week, followed by nasal cannula
for the next 3 weeks. She is now 5 weeks old, in room air, on full enteral feedings, and
receiving daily caffeine. She has intermittent episodes of apnea and bradycardia,
approximately 3 or 4 times a day, which typically self-resolve. Which of the following
treatments is most appropriate for the management of apnea of prematurity for this
patient?

Vol. 18 No. 3 MARCH 2017 e159

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 A. If the infant is on full enteral feedings, an antireflux medication is indicated.
B. High-flow nasal cannula with a fraction of inspired oxygen of 1.0 is indicated until
there are no more apnea events.
C. Continued use of caffeine is indicated if the infant is continuing to have events.
D. As the patient is still having events while receiving caffeine, a blood transfusion
followed by doxopram is indicated.
E. A continuous theophylline drip can be started and continued for 1 week to facilitate
symptom resolution.
5. A 27-week gestational age male infant is being discharged from the hospital after 10 weeks
in the NICU. He had apnea of prematurity that was treated with caffeine. The caffeine was
discontinued 3 weeks ago and his last noted apnea event was 2 weeks ago. The parents ask
whether they should be worried about the possibility of sudden infant death syndrome
(SIDS). Which of the following statements regarding this possibility is correct?
A. The number of episodes of apnea in the NICU for preterm infants directly correlates
to increased risk of SIDS after discharge.
B. Routine home monitoring to decrease the incidence of SIDS is recommended for
patients born before 28 weeks’ gestational age.
C. On average, apnea of prematurity typically resolves at a later date than the
occurrence of SIDS in extremely preterm infants.
D. Infants born preterm with history of apnea of prematurity have been noted to have
higher baseline heart rates and lower heart rate variability in the first several
months after birth, which is similar to findings in infants who died of SIDS.
E. Hospital readmission in the first 2 months after initial discharge is linked to both
increased risk of apnea events during the first hospitalization and the risk of SIDS.

e160 NeoReviews
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 Apnea of Prematurity: Current Practices and Future Directions
Kalpashri Kesavan and Joanna Parga
NeoReviews 2017;18;e149
DOI: 10.1542/neo.18-3-e149

Updated Information & including high resolution figures, can be found at:
Services http://neoreviews.aappublications.org/content/18/3/e149
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http://neoreviews.aappublications.org/content/18/3/e149#BIBL
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 Apnea of Prematurity: Current Practices and Future Directions
Kalpashri Kesavan and Joanna Parga
NeoReviews 2017;18;e149
DOI: 10.1542/neo.18-3-e149

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://neoreviews.aappublications.org/content/18/3/e149

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