Brief Resolved Unexplained Events (Formerly Apparent Life-Threatening Events) and Evaluation of Lower-Risk Infants - American Academy of ...
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CLINICAL PRACTICE GUIDELINE Guidance for the Clinician in Rendering Pediatric Care
Brief Resolved Unexplained
Events (Formerly Apparent
Life-Threatening Events) and
Evaluation of Lower-Risk Infants
Joel S. Tieder, MD, MPH, FAAP, Joshua L. Bonkowsky, MD, PhD, FAAP, Ruth A. Etzel, MD, PhD, FAAP, Wayne
H. Franklin, MD, MPH, MMM, FAAP, David A. Gremse, MD, FAAP, Bruce Herman, MD, FAAP, Eliot S. Katz,
MD, FAAP, Leonard R. Krilov, MD, FAAP, J. Lawrence Merritt II, MD, FAAP, Chuck Norlin, MD, FAAP, Jack
Percelay, MD, MPH, FAAP, Robert E. Sapién, MD, MMM, FAAP, Richard N. Shiffman, MD, MCIS, FAAP, Michael
B.H. Smith, MB, FRCPCH, FAAP, for the SUBCOMMITTEE ON APPARENT LIFE THREATENING EVENTS
This is the first clinical practice guideline from the American Academy of abstract
Pediatrics that specifically applies to patients who have experienced an
apparent life-threatening event (ALTE). This clinical practice guideline has
3 objectives. First, it recommends the replacement of the term ALTE with a
new term, brief resolved unexplained event (BRUE). Second, it provides an
approach to patient evaluation that is based on the risk that the infant will
have a repeat event or has a serious underlying disorder. Finally, it provides
management recommendations, or key action statements, for lower-risk
infants. The term BRUE is defined as an event occurring in an infant younger
This document is copyrighted and is property of the American
than 1 year when the observer reports a sudden, brief, and now resolved Academy of Pediatrics and its Board of Directors. All authors have
episode of ≥1 of the following: (1) cyanosis or pallor; (2) absent, decreased, filed conflict of interest statements with the American Academy
of Pediatrics. Any conflicts have been resolved through a process
or irregular breathing; (3) marked change in tone (hyper- or hypotonia); and approved by the Board of Directors. The American Academy of
Pediatrics has neither solicited nor accepted any commercial
(4) altered level of responsiveness. A BRUE is diagnosed only when there is involvement in the development of the content of this publication.
no explanation for a qualifying event after conducting an appropriate history The guidance in this report does not indicate an exclusive course of
and physical examination. By using this definition and framework, infants treatment or serve as a standard of medical care. Variations, taking
into account individual circumstances, may be appropriate.
younger than 1 year who present with a BRUE are categorized either as (1)
All clinical practice guidelines from the American Academy of
a lower-risk patient on the basis of history and physical examination for Pediatrics automatically expire 5 years after publication unless
whom evidence-based recommendations for evaluation and management reaffirmed, revised, or retired at or before that time.
are offered or (2) a higher-risk patient whose history and physical DOI: 10.1542/peds.2016-0590
examination suggest the need for further investigation and treatment but PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
for whom recommendations are not offered. This clinical practice guideline Copyright © 2016 by the American Academy of Pediatrics
is intended to foster a patient- and family-centered approach to care, reduce
unnecessary and costly medical interventions, improve patient outcomes,
support implementation, and provide direction for future research. Each key To cite: Tieder JS, Bonkowsky JL, Etzel RA, et al. Brief
Resolved Unexplained Events (Formerly Apparent Life-
action statement indicates a level of evidence, the benefit-harm relationship, Threatening Events) and Evaluation of Lower-Risk Infants.
and the strength of recommendation. Pediatrics. 2016;137(5):e20160590
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PEDIATRICS Volume 137, number 5, May 2016:e20160590 FROM THE AMERICAN ACADEMY OF PEDIATRICSINTRODUCTION constellation of observed, subjective, or death. Yet, the perceived
and nonspecific symptoms, has raised potential for recurring events or a
This clinical practice guideline
significant challenges for clinicians serious underlying disorder often
applies to infants younger than 1
and parents in the evaluation and provokes concern in caregivers
year and is intended for pediatric
care of these infants.3 Although and clinicians.2,4,5 This concern can
clinicians. This guideline has
a broad range of disorders can compel testing or admission to the
3 primary objectives. First, it
present as an ALTE (eg, child abuse, hospital for observation, which
recommends the replacement of
congenital abnormalities, epilepsy, can increase parental anxiety and
the term apparent life-threatening
inborn errors of metabolism, and subject the patient to further risk
event (ALTE) with a new term,
infections), for a majority of infants and does not necessarily lead to a
brief resolved unexplained event
who appear well after the event, the treatable diagnosis or prevention
(BRUE). Second, it provides an
risk of a serious underlying disorder of future events. A more precise
approach to patient evaluation that
or a recurrent event is extremely definition could prevent the overuse
is based on the risk that the infant
low.2 of medical interventions by helping
will have a recurring event or has
clinicians distinguish infants with
a serious underlying disorder.
lower risk. Finally, the use of ALTE
Third, it provides evidence-based CHANGE IN TERMINOLOGY AND as a diagnosis may reinforce the
management recommendations, or DIAGNOSIS caregivers’ perceptions that the
key action statements, for lower-risk
The imprecise nature of the original event was indeed “life-threatening,”
patients whose history and physical
ALTE definition is difficult to apply even when it most often was not.
examination are normal. It does not
to clinical care and research.3 For these reasons, a replacement of
offer recommendations for higher-
As a result, the clinician is often the term ALTE with a more specific
risk patients whose history and
faced with several dilemmas. First, term could improve clinical care and
physical examination suggest the
under the ALTE definition, the management.
need for further investigation and
infant is often, but not necessarily,
treatment (because of insufficient
asymptomatic on presentation. In this clinical practice guideline, a
evidence or the availability of
The evaluation and management more precise definition is introduced
clinical practice guidelines specific
of symptomatic infants (eg, those for this group of clinical events: brief
to their presentation). This clinical
with fever or respiratory distress) resolved unexplained event (BRUE).
practice guideline also provides
need to be distinguished from that The term BRUE is intended to better
implementation support and suggests
of asymptomatic infants. Second, the reflect the transient nature and lack
directions for future research.
reported symptoms under the ALTE of clear cause and removes the “life-
The term ALTE originated from a definition, although often concerning threatening” label. The authors of
1986 National Institutes of Health to the caregiver, are not intrinsically this guideline recommend that the
Consensus Conference on Infantile life-threatening and frequently are term ALTE no longer be used by
Apnea and was intended to replace a benign manifestation of normal clinicians to describe an event or as
the term “near-miss sudden infant infant physiology or a self-limited a diagnosis. Rather, the term BRUE
death syndrome” (SIDS).1 An condition. A definition needs enough should be used to describe events
ALTE was defined as “an episode precision to allow the clinician to occurring in infants younger than
that is frightening to the observer base clinical decisions on events that 1 year of age that are characterized
and that is characterized by some are characterized as abnormal after by the observer as “brief” (lasting
combination of apnea (central or conducting a thorough history andan appropriate history and physical TABLE 1 BRUE Definition and Factors for Inclusion and Exclusion examination. Similarly, an event Includes Excludes characterized as choking or gagging Brief Duration
hypertonia or hypotonia. Seventh, TABLE 2 Historical Features To Be Considered in the Evaluation of a Potential BRUE
because choking and gagging usually Features To Be Considered
indicate common diagnoses such as Considerations for possible child abuse:
GER or respiratory infection, their Multiple or changing versions of the history/circumstances
presence suggests an event was History/circumstances inconsistent with child’s developmental stage
not a BRUE. Finally, the use of History of unexplained bruising
Incongruence between caregiver expectations and child’s developmental stage, including assigning
“altered level of responsiveness” is a
negative attributes to the child
new criterion, because it can History of the event
be an important component of General description
an episodic but serious cardiac, Who reported the event?
respiratory, metabolic, or neurologic Witness of the event? Parent(s), other children, other adults? Reliability of historian(s)?
State immediately before the event
event.
Where did it occur (home/elsewhere, room, crib/floor, etc)?
Awake or asleep?
For infants who have experienced a
Position: supine, prone, upright, sitting, moving?
BRUE, a careful history and physical Feeding? Anything in the mouth? Availability of item to choke on? Vomiting or spitting up?
examination are necessary to Objects nearby that could smother or choke?
characterize the event, assess the State during the event
risk of recurrence, and determine Choking or gagging noise?
Active/moving or quiet/flaccid?
the presence of an underlying
Conscious? Able to see you or respond to voice?
disorder (Tables 2 and 3). The Muscle tone increased or decreased?
recommendations provided in this Repetitive movements?
guideline focus on infants with a Appeared distressed or alarmed?
lower risk of a subsequent event or Breathing: yes/no, struggling to breathe?
Skin color: normal, pale, red, or blue?
serious underlying disorder (see
Bleeding from nose or mouth?
section entitled “Risk Assessment: Color of lips: normal, pale, or blue?
Lower- Versus Higher-Risk BRUE”). End of event
In the absence of identifiable risk Approximate duration of the event?
factors, infants are at lower risk and How did it stop: with no intervention, picking up, positioning, rubbing or clapping back, mouth-to-
mouth, chest compressions, etc?
laboratory studies, imaging studies,
End abruptly or gradually?
and other diagnostic procedures are Treatment provided by parent/caregiver (eg, glucose-containing drink or food)?
unlikely to be useful or necessary. 911 called by caregiver?
However, if the clinical history State after event
or physical examination reveals Back to normal immediately/gradually/still not there?
Before back to normal, was quiet, dazed, fussy, irritable, crying?
abnormalities, the patient may
Recent history
be at higher risk and further Illness in preceding day(s)?
evaluation should focus on the If yes, detail signs/symptoms (fussiness, decreased activity, fever, congestion, rhinorrhea, cough,
specific areas of concern. For vomiting, diarrhea, decreased intake, poor sleep)
example, Injuries, falls, previous unexplained bruising?
Past medical history
• possible child abuse may be Pre-/perinatal history
considered when the event Gestational age
Newborn screen normal (for IEMs, congenital heart disease)?
history is reported inconsistently
Previous episodes/BRUE?
or is incompatible with the Reflux? If yes, obtain details, including management
child’s developmental age, or Breathing problems? Noisy ever? Snoring?
when, on physical examination, Growth patterns normal?
there is unexplained bruising Development normal? Assess a few major milestones across categories, any concerns about
development or behavior?
or a torn labial or lingual
Illnesses, injuries, emergencies?
frenulum; Previous hospitalization, surgery?
Recent immunization?
• a cardiac arrhythmia may be
Use of over-the-counter medications?
considered if there is a family Family history
history of sudden, unexplained Sudden unexplained death (including unexplained car accident or drowning) in first- or second-
death in first-degree relatives; and degree family members before age 35, and particularly as an infant?
Apparent life-threatening event in sibling?
• infection may be considered Long QT syndrome?
if there is fever or persistent Arrhythmia?
respiratory symptoms.
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e4 FROM THE AMERICAN ACADEMY OF PEDIATRICSTABLE 2 Continued • Prematurity: gestational age ≥32
Features To Be Considered weeks and postconceptional age
Inborn error of metabolism or genetic disease? ≥45 weeks
Developmental delay?
Environmental history
• First BRUE (no previous BRUE ever
Housing: general, water damage, or mold problems? and not occurring in clusters)
Exposure to tobacco smoke, toxic substances, drugs? • Duration of eventTABLE 3 Physical Examination Features To Be Considered in the Evaluation of a Potential BRUE the Society of Hospital Medicine’s
Physical Examination ALTE Expert Panel (which included
General appearance
4 members of the subcommittee).3
Craniofacial abnormalities (mandible, maxilla, nasal) The subcommittee partnered with
Age-appropriate responsiveness to environment the Society of Hospital Medicine
Growth variables Expert Panel and a librarian to
Length, weight, occipitofrontal circumference
update the original systematic
Vital signs
Temperature, pulse, respiratory rate, blood pressure, oxygen saturation review with articles published
Skin through December 31, 2014, with
Color, perfusion, evidence of injury (eg, bruising or erythema) the use of the same methodology
Head as the original systematic review.
Shape, fontanelles, bruising or other injury
PubMed, Cumulative Index to
Eyes
General, extraocular movement, pupillary response Nursing and Allied Health Literature,
Conjunctival hemorrhage and Cochrane Library databases
Retinal examination, if indicated by other findings were searched for studies involving
Ears children younger than 24 months
Tympanic membranes
by using the stepwise approach
Nose and mouth
Congestion/coryza specified in the Preferred Reporting
Blood in nares or oropharynx Items for Systematic Reviews and
Evidence of trauma or obstruction Meta-Analyses (PRISMA) statement.8
Torn frenulum Search terms included “ALTE(s),”
Neck
Mobility
“apparent life threatening event(s),”
Chest “life threatening event(s),” “near
Auscultation, palpation for rib tenderness, crepitus, irregularities miss SIDS” or “near miss sudden
Heart infant death syndrome,” “aborted
Rhythm, rate, auscultation
crib death” or “aborted sudden infant
Abdomen
Organomegaly, masses, distention death syndrome,” and “aborted SIDS”
Tenderness or “aborted cot death” or “infant
Genitalia death, sudden.” The Medical Subject
Any abnormalities Heading “infantile apparent life-
Extremities
threatening event,” introduced in
Muscle tone, injuries, limb deformities consistent with fracture
Neurologic 2011, was also searched but did not
Alertness, responsiveness identify additional articles.
Response to sound and visual stimuli
General tone In updating the systematic
Pupillary constriction in response to light review published in 2012, pairs
Presence of symmetrical reflexes of 2 subcommittee members
Symmetry of movement/tone/strength
used validated methodology to
independently score the newly
and experts in the fields of general members repeated this process identified abstracts from English-
pediatrics, hospital medicine, annually and upon publication of the language articles (n = 120) for
emergency medicine, infectious guideline. All potential conflicts of relevance to the clinical questions
diseases, child abuse, sleep medicine, interest are listed at the end of this (Supplemental Fig 3).9,10 Two
pulmonary medicine, cardiology, document. The project was funded by independent reviewers then critically
neurology, biochemical genetics, the AAP. appraised the full text of the
gastroenterology, environmental identified articles (n = 23) using
health, and quality improvement. The subcommittee performed a structured data collection form
The subcommittee also included a a comprehensive review of the based on published guidelines for
parent representative, a guideline literature related to ALTEs from evaluating medical literature.11,12
methodologist/informatician, and an 1970 through 2014. Articles They recorded each study’s
epidemiologist skilled in systematic from 1970 through 2011 were relevance to the clinical question,
reviews. All panel members declared identified and evaluated by using research design, setting, time
potential conflicts on the basis of the “Management of Apparent Life period covered, sample size, patient
AAP policy on Conflict of Interest and Threatening Events in Infants: A eligibility criteria, data source,
Voluntary Disclosure. Subcommittee Systematic Review,” authored by variables collected, key results, study
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e6 FROM THE AMERICAN ACADEMY OF PEDIATRICSFIGURE 1
Diagnosis, risk classification, and recommended management of a BRUE. *See Tables 3 and 4 for the determination of an appropriate and negative FH
and PE. **See Fig 2 for the AAP method for rating of evidence and recommendations. CSF, cerebrospinal fluid; FH, family history; PE, physical examination;
WBC, white blood cell.
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PEDIATRICS Volume 137, number 5, May 2016 e7a systematic grading of the quality
of evidence from the updated
literature review by 2 independent
reviewers and incorporation of
the previous systematic review.
Expert consensus was used when
definitive data were not available.
If committee members disagreed
with the rest of the consensus, they
were encouraged to voice their
concern until full agreement was
reached. If full agreement could not
be reached, each committee member
reserved the right to state concern
or disagreement in the publication
(which did not occur). Because the
recommendations of this guideline
were based on the ALTE literature,
we relied on the studies and
outcomes that could be attributable
to the new definition of lower- or
higher-risk BRUE patients.
Key action statements (summarized
FIGURE 2 in Table 5) were generated by
AAP rating of evidence and recommendations. using BRIDGE-Wiz (Building
Recommendations in a Developers
limitations, potential sources of bias, in the updated (n = 18) and Guideline Editor), an interactive
and stated conclusions. If at least original (n = 37) systematic review software tool that leads guideline
1 reviewer judged an article to be (Supplemental Table 7).6,7,13–28 development teams through a series
relevant on the basis of the full text, The resulting systematic review of questions that are intended
subsequently at least 2 reviewers was used to develop the guideline to create clear, transparent, and
critically appraised the article and recommendations by following actionable key action statements.30
determined by consensus what the policy statement from the AAP BRIDGE-Wiz integrates the quality
evidence, if any, should be cited Steering Committee on Quality of available evidence and a benefit-
in the systematic review. Selected Improvement and Management, harm assessment into the final
articles used in the earlier review “Classifying Recommendations determination of the strength of each
were also reevaluated for their for Clinical Practice Guidelines.”29 recommendation. Evidence-based
quality. The final recommendations Decisions and the strength of guideline recommendations from
were based on articles identified recommendations were based on the AAP may be graded as strong,
TABLE 4 Guideline Definitions for Key Action Statements
Statement Definition Implication
Strong recommendation A particular action is favored because anticipated benefits Clinicians should follow a strong recommendation
clearly exceed harms (or vice versa) and quality of unless a clear and compelling rationale for an
evidence is excellent or unobtainable. alternative approach is present.
Moderate recommendation A particular action is favored because anticipated benefits Clinicians would be prudent to follow a moderate
clearly exceed harms (or vice versa) and the quality of recommendation but should remain alert to new
evidence is good but not excellent (or is unobtainable). information and sensitive to patient preferences.
Weak recommendation (based on low- A particular action is favored because anticipated benefits Clinicians would be prudent follow a weak
quality evidence) clearly exceed harms (or vice versa), but the quality of recommendation but should remain alert to new
evidence is weak. information and very sensitive to patient preferences.
Weak recommendation (based on Weak recommendation is provided when the aggregate Clinicians should consider the options in their
balance of benefits and harms) database shows evidence of both benefit and harm that decision-making, but patient preference may have a
appear to be similar in magnitude for any available substantial role.
courses of action.
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e8 FROM THE AMERICAN ACADEMY OF PEDIATRICSTABLE 5 Summary of Key Action Statements for Lower-Risk BRUEs When managing an infant aged >60 d and
1A. Clinicians Need Not Admit Infants Presenting With a Lower-Risk BRUE to the management of BRUEs but rather
Hospital Solely for Cardiorespiratory Monitoring (Grade B, Weak Recommendation) is intended to assist clinicians by
providing a framework for clinical
Aggregate Evidence Quality Grade B
Benefits Reduce unnecessary testing and caregiver/infant anxiety decision-making.
Avoid consequences of false-positive result, health care–
associated infections, and other KEY ACTION STATEMENTS FOR LOWER-
patient safety risks
RISK BRUE
Risks, harm, cost May rarely miss a recurrent event or diagnostic opportunity
for rare underlying condition
Benefit-harm assessment The benefits of reducing unnecessary testing, nosocomial
1. Cardiopulmonary
infections, and false-positive results, 1A. Clinicians Need Not Admit
as well as alleviating caregiver and infant anxiety, Infants Presenting With a Lower-
outweigh the rare missed diagnostic
Risk BRUE to the Hospital Solely for
opportunity for an underlying condition
Intentional vagueness None
Cardiorespiratory Monitoring (Grade B,
Role of patient preferences Caregiver anxiety and access to quality follow-up care may Weak Recommendation)
be important considerations in determining whether a Infants presenting with an
hospitalization for cardiovascular monitoring is indicated
Exclusions None
ALTE often have been admitted
Strength Weak recommendation (because of equilibrium between for observation and testing.
benefits and harms) Observational data indicate that 12%
Key references 31, 32 to 14% of infants presenting with a
diagnosis of ALTE had a subsequent
event or condition that required
1B. Clinicians May Briefly Monitor Infants Presenting With a Lower-Risk BRUE hospitalization.7,31 Thus, research
With Continuous Pulse Oximetry and Serial Observations (Grade D, Weak has sought to identify risk factors
Recommendation) that could be used to identify infants
likely to benefit from hospitalization.
Aggregate Evidence Quality Grade D
A long-term follow-up study in
Benefits Identification of hypoxemia
Risks, harm, cost Increased costs due to monitoring over time and the use of hospital infants hospitalized with an ALTE
resources showed that no infants subsequently
False-positive results may lead to subsequent testing and had SIDS but 11% were victims of
hospitalization child abuse and 4.9% had adverse
False reassurance from negative test results
neurologic outcomes (see 3.
Benefit-harm assessment The potential benefit of detecting hypoxemia outweighs the harm of
cost and false results Neurology).32 The ALTE literature
Intentional vagueness Duration of time to monitor patients with continuous pulse oximetry supports that infants presenting with
and the number and frequency of serial observations may vary a lower-risk BRUE do not have an
Role of patient preferences Level of caregiver concern may influence the duration of oximetry increased rate of cardiovascular or
monitoring
other events during admission and
Exclusions None
Strength Weak recommendation (based on low quality of evidence) hospitalization may not be required,
Key references 33, 36
but close follow-up is recommended.
Careful outpatient follow-up is
advised (repeat clinical history and
decision-making, particularly when All comments were reviewed by the physical examination within 24
recommendations are expressed subcommittee and incorporated into hours after the initial evaluation) to
as weak. Key action statements the final guideline when appropriate. identify infants with ongoing medical
based on that evidence and expert concerns that would indicate further
This guideline is intended for use
consensus are provided. A summary evaluation and treatment.
primarily by clinicians providing
is provided in Table 5. care for infants who have Al-Kindy et al33 used documented
The practice guideline underwent experienced a BRUE and their monitoring in 54% of infants
a comprehensive review by families. This guideline may be of admitted for an ALTE (338 of 625)
stakeholders before formal interest to parents and payers, but and identified 46 of 338 (13.6%)
approval by the AAP, including AAP it is not intended to be used for with “extreme” cardiovascular events
councils, committees, and sections; reimbursement or to determine (central apnea >30 seconds, oxygen
selected outside organizations; insurance coverage. This guideline saturationof postconceptional age). However, well documented.33,35 However, the respiratory tract.37 Most, but not
no adverse outcomes were noted significance of these brief hypoxemic all, infants with significant lower
for any of their cohort (although events has not been established. respiratory tract infections will be
whether there is a protective effect symptomatic at the time of ALTE
1B. Clinicians May Briefly Monitor presentation. However, 2 studies
of observation alone is not known).
Infants Presenting With a Lower-Risk
Some of the infants with extreme have documented pneumonia in
BRUE With Continuous Pulse Oximetry
events developed symptoms of and Serial Observations (Grade D, Weak infants presenting with ALTE and an
upper respiratory infection 1 to 2 Recommendation) otherwise noncontributory history
days after the ALTE presentation. and physical examination.4,37 These
A normal physical examination, rare exceptions have generally been
The risk factors for “extreme” events
including vital signs and oximetry, in infants younger than 2 months
were prematurity, postconceptional
is needed for a patient who has and would have placed them in the
age 48 weeks Gupta38 reported that 9 of 65 patients
as a longer interval of observation. (ages unknown) who had ALTEs had
were not documented as having Unfortunately, there are few data
an extreme event in this cohort. A abnormalities on chest radiography
to suggest the optimal duration (not fully specified) despite no
previous longitudinal study also of this period, the value of repeat
identified “extreme” events that suspected respiratory disorder
examinations, and the effect of on clinical history or physical
occurred with comparable frequency false-positive evaluations on family-
in otherwise normal term infants and examination. Some of the radiographs
centered care. Several studies have were performed up to 24 hours
that were not statistically increased documented intermittent episodes of
in term infants with a history of after presentation. Davies and Gupta
hypoxemia after admission for further reported that 33% of infants
ALTE.34 ALTE.7,31,33 Pulse oximetry with ALTEs that were ultimately
identified more infants with associated with a respiratory disease
Preterm infants have been shown concerning paroxysmal events had a normal initial respiratory
to have more serious events, than cardiorespiratory monitoring examination.38 Kant et al18 reported
although an ALTE does not further alone.33 However, occasional oxygen that 2 of 176 infants discharged
increase that risk compared with desaturations are commonly observed after admission for ALTE died within
asymptomatic preterm infants in normal infants, especially during 2 weeks, both of pneumonia. One
without ALTE.34 Claudius and sleep.36 Furthermore, normative infant had a normal chest radiograph
Keens31 performed an observational oximetry data are dependent on the initially; the other, with a history
prospective study in 59 infants specific machine, averaging interval, of prematurity, had a “possible”
presenting with ALTE who had been altitude, behavioral state, and infiltrate. Thus, most experience
born at >30 weeks’ gestation and postconceptional age. Similarly, there has shown that a chest radiograph
had no significant medical illness. may be considerable variability in the in otherwise well-appearing infants
They evaluated factors in the clinical vital signs and the clinical appearance rarely alters clinical management.7
history and physical examination of an infant. Pending further research Careful follow-up within 24 hours
that, according to the authors, would into this important issue, clinicians is important in infants with a
warrant hospital admission on the may choose to monitor and provide nonfocal clinical history and physical
basis of adverse outcomes (including serial examinations of infants in the examination to identify those
recurrent cardiorespiratory events, lower-risk group for a brief period who will ultimately have a lower
infection, child abuse, or any life- of time, ranging from 1 to 4 hours, to respiratory tract infection diagnosed.
threatening condition). Among these establish that the vital signs, physical
otherwise well infants, those with examination, and symptomatology 1D. Clinicians Should Not Obtain
multiple ALTEs or age1C. Clinicians Should Not Obtain Chest Radiograph in Infants Presenting With a are predictive of ensuing events over
Lower-Risk BRUE (Grade B, Moderate Recommendation) the next several months.40 However,
without a control population, the
Aggregate Evidence Quality Grade B
Benefits Reduce costs, unnecessary testing, radiation exposure, and clinical significance of these events
caregiver/infant anxiety is uncertain, because respiratory
Avoid consequences of false-positive results pauses are frequently observed in
Risks, harm, cost May rarely miss diagnostic opportunity for early lower otherwise normal infants.35 Similarly,
respiratory tract or cardiac disease
Benefit-harm assessment The benefits of reducing unnecessary testing, radiation
Kahn and Blum41 reported that 10
exposure, and false-positive results, as well as alleviating of 71 infants with a clinical history
caregiver and infant anxiety, outweigh the rare missed of “benign” ALTEs had an abnormal
diagnostic opportunity for lower respiratory tract or cardiac polysomnograph, including periodic
disease breathing (7 of 10) or obstructive
Intentional vagueness None
apnea (4 of 100), but specific data
Role of patient preferences Caregiver may express concern regarding a longstanding
were not presented. These events
breathing pattern in his/her infant or a recent change in
breathing that might influence the decision to obtain chest were not found in a control group
radiography of 181 infants. The severity of the
Exclusions None periodic breathing (frequency
Strength Moderate recommendation of arousals and extent of oxygen
Key references 4, 37 desaturation) could not be evaluated
from these data. Daniëls et al42
performed polysomnography in
1D. Clinicians Should Not Obtain Measurement of Venous or Arterial Blood Gases in 422 infants with ALTEs and
Infants Presenting With a Lower-Risk BRUE (Grade B, Moderate Recommendation) identified 11 infants with significant
bradycardia, OSA, and/or oxygen
Aggregate Evidence Quality Grade B
Benefits Reduce costs, unnecessary testing, pain, risk of thrombosis, and
desaturation. Home monitoring
caregiver/infant anxiety revealed episodes of bradycardia
Avoid consequences of false-positive results (20 seconds for OSA should be guided by an
end-tidal carbon dioxide, chest/ or brief episodes of bradycardia that assessment of risk on the basis of a
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e12 FROM THE AMERICAN ACADEMY OF PEDIATRICS1E. Clinicians Should Not Obtain an Overnight Polysomnograph in Infants Presenting 1F. Clinicians May Obtain a 12-Lead
With a Lower-Risk BRUE (Grade B, Moderate Recommendation) Electrocardiogram for Infants
Presenting With Lower-Risk BRUE
Aggregate Evidence Quality Grade B (Grade C, Weak Recommendation)
Benefits Reduce costs, unnecessary testing, and caregiver/infant anxiety
Avoid consequences of false-positive results ALTE studies have examined
Risks, harm, cost May miss rare instances of hypoxemia, hypercapnia, and/or screening electrocardiograms
bradycardia that would be detected by polysomnography
(ECGs). A study by Brand et al4 found
Benefit-harm assessment The benefits of reducing unnecessary testing and false-positive
results, as well as alleviating caregiver and infant anxiety, no positive findings on 24 ECGs
outweigh the rare missed diagnostic opportunity for hypoxemia, performed on 72 patients (33%)
hypercapnia, and/or bradycardia without a contributory history or
Intentional vagueness None physical examination. Hoki et al16
Role of patient preferences Caregivers may report concern regarding some aspects of
reported a 4% incidence of cardiac
their infant’s sleep pattern that may influence the decision to
perform polysomnography disease found in 485 ALTE patients;
Exclusions None ECGs were performed in 208 of 480
Strength Moderate recommendation patients (43%) with 3 of 5 abnormal
Key reference 39 heart rhythms identified by the
ECG and the remaining 2 showing
structural heart disease. Both studies
1F. Clinicians May Obtain a 12-Lead Electrocardiogram for Infants Presenting With had low positive-predictive values
Lower-Risk BRUE (Grade C, Weak Recommendation) of ECGs (0% and 1%, respectively).
Aggregate Evidence Quality Grade C Hoki et al had a negative predictive
Benefits May identify BRUE patients with channelopathies (long QT syndrome, value of 100% (96%–100%), and
short QT syndrome, and Brugada syndrome), ventricular pre- given the low prevalence of disease,
excitation (Wolff-Parkinson-White syndrome), cardiomyopathy, or there is little need for further testing
other heart disease
Risks, harm, cost False-positive results may lead to further workup, expert consultation, in patients with a negative ECG.
anxiety, and cost
False reassurance from negative results Some cardiac conditions that
Cost and availability of electrocardiography testing and interpretation
may present as a BRUE include
channelopathies (long QT syndrome,
Benefit-harm assessment The benefit of identifying patients at risk of sudden cardiac death
outweighs the risk of cost and false results short QT syndrome, Brugada
Intentional vagueness None syndrome, and catecholaminergic
Role of patient preferences Caregiver may decide not to have testing performed polymorphic ventricular
Exclusions None tachycardia), ventricular pre-
Strength Weak recommendation (because of equilibrium between benefits and excitation (Wolff-Parkinson-White
harms) syndrome), and cardiomyopathy/
Key references 4, 16 myocarditis (hypertrophic
cardiomyopathy, dilated
cardiomyopathy). Resting ECGs are
comprehensive clinical history and may be asymptomatic and have ineffective in identifying patients
physical examination.50 Symptoms of a normal physical examination.54 with catecholaminergic polymorphic
OSA, which may be subtle or absent However, some studies have ventricular tachycardia. Family
in infants, include snoring, noisy reported a high incidence of snoring history is important in identifying
respirations, labored breathing, in infants with (26%–44%) and individuals with channelopathies.
mouth breathing, and profuse without (22%–26%) OSA, making
sweating.51 Occasionally, infants the distinction difficult.55 Additional Severe potential outcomes of any of
with OSA will present with failure risk factors for infant OSA include these conditions, if left undiagnosed
to thrive, witnessed apnea, and/ prematurity, maternal smoking, or untreated, include sudden death
or developmental delay.52 Snoring bronchopulmonary dysplasia, or neurologic injury.59 However,
may be absent in younger infants obesity, and specific medical many patients do not ever experience
with OSA, including those with conditions including laryngomalacia, symptoms in their lifetime and
micrognathia. In addition, snoring in craniofacial abnormalities, adverse outcomes are uncommon.
otherwise normal infants is present neuromuscular weakness, Down A genetic autopsy study in infants
at least 2 days per week in 11.8% syndrome, achondroplasia, Chiari who died of SIDS in Norway showed
and at least 3 days per week in 5.3% malformations, and Prader-Willi an association between 9.5% and
of infants.53 Some infants with OSA syndrome.34,56–58 13.0% of infants with abnormal
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PEDIATRICS Volume 137, number 5, May 2016 e131G. Clinicians Should Not Obtain an Echocardiogram in Infants Presenting With 32 echocardiograms in 243 ALTE
Lower-Risk BRUE (Grade C, Moderate Recommendation) patients and found only 1 abnormal
echocardiogram, which was
Aggregate Evidence Quality Grade C
Benefits Reduce costs, unnecessary testing, caregiver/infant anxiety, and suspected because of an abnormal
sedation risk history and physical examination
Avoid consequences of false-positive results (double aortic arch).
Risks, harm, cost May miss rare diagnosis of cardiac disease
Benefit-harm assessment The benefits of reducing unnecessary testing and sedation risk, as 1H. Clinicians Should Not Initiate Home
well as alleviating caregiver and infant anxiety, outweigh the rare Cardiorespiratory Monitoring in Infants
missed diagnostic opportunity for cardiac causes
Presenting With a Lower-Risk BRUE
Intentional vagueness Abnormal cardiac physical examination reflects the clinical judgment
of the clinician
(Grade B, Moderate Recommendation)
Role of patient preferences Some caregivers may prefer to have echocardiography performed The use of ambulatory
Exclusions Patients with an abnormal cardiac physical examination
cardiorespiratory monitors in infants
Strength Moderate recommendation
Key references 4, 16 presenting with ALTEs has been
proposed as a modality to identify
subsequent events, reduce the risk
1H. Clinicians Should Not Initiate Home Cardiorespiratory Monitoring in Infants of SIDS, and alert caregivers of the
Presenting With a Lower-Risk BRUE (Grade B, Moderate Recommendation) need for intervention. Monitors
Aggregate Evidence Quality Grade B can identify respiratory pauses
Benefits Reduce costs, unnecessary testing, and caregiver/infant anxiety and bradycardia in many infants
Avoid consequences of false-positive results presenting with ALTE; however,
Risks, harm, cost May rarely miss an infant with recurrent central apnea or cardiac these events are also occasionally
arrhythmias observed in otherwise normal
Benefit-harm assessment The benefits of reducing unnecessary testing and false-positive
infants.34,40 In addition, infant
results, as well as alleviating caregiver and infant anxiety,
outweigh the rare missed diagnostic opportunity for recurrent monitors are prone to artifact and
apnea or cardiac arrhythmias have not been shown to improve
Intentional vagueness None outcomes or prevent SIDS or improve
Role of patient preferences Caregivers will frequently request monitoring be instituted after an neurodevelopmental outcomes.63
ALTE in their infant; a careful explanation of the limitations and Indeed, caregiver anxiety may be
disadvantages of this technology should be given
exacerbated with the use of infant
Exclusions None
monitors and potential false alarms.
Strength Moderate recommendation
The overwhelming majority of
Key reference 34
monitor-identified alarms, including
many with reported clinical
or novel gene findings at the long myocarditis could rarely present symptomatology, do not reveal
QT loci.60 A syncopal episode, as a lower-risk BRUE and can be abnormalities on cardiorespiratory
which could present as a BRUE, is identified with echocardiography. recordings.64–66 Finally, there are
strongly associated with subsequent The cost of an echocardiogram is high several studies showing a lack of
sudden cardiac arrest in patients and accompanied by sedation risks. correlation between ALTEs and
with long QT syndrome.61 The SIDS.24,32
incidence and risk in those with In a study in ALTE patients,
other channelopathies have not been Hoki et al16 did not recommend Kahn and Blum41 monitored 50
adequately studied. The incidence echocardiography as an initial infants considered at “high risk” of
of sudden cardiac arrest in patients cardiac test unless there are SIDS and reported that 80% had
with ventricular pre-excitation findings on examination or from alarms at home. All infants with
(Wolff-Parkinson-White syndrome) an echocardiogram consistent alarms had at least 1 episode of
is 3% to 4% over the lifetime of the with heart disease. The majority of parental intervention motivated by
individual.62 abnormal echocardiogram findings the alarms, although the authors
in their study were not perceived acknowledged that some cases of
1G. Clinicians Should Not Obtain an to be life-threatening or related parental intervention may have been
Echocardiogram in Infants Presenting to a cause for the ALTE (eg, septal attributable to parental anxiety.
With Lower-Risk BRUE (Grade C, defects or mild valve abnormalities), Nevertheless, the stimulated infants
Moderate Recommendation) and they would have been detected did not die of SIDS or require
Cardiomyopathy (hypertrophic on echocardiogram or physical rehospitalization and therefore
and dilated cardiomyopathy) and examination. Brand et al4 reported it was concluded that monitoring
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e14 FROM THE AMERICAN ACADEMY OF PEDIATRICSresulted in successful resuscitation, 2A. Clinicians Need Not Obtain Neuroimaging (Computed Tomography, MRI, or
but this was not firmly established. Ultrasonography) To Detect Child Abuse in Infants Presenting With a Lower-Risk
Côté et al40 reported “significant BRUE (Grade C, Weak Recommendation)
events” involving central apnea Aggregate Evidence Quality Grade C
and bradycardia with long-term Benefits Decrease cost
monitoring. However, these events Avoid sedation, radiation exposure, consequences of false-
were later shown to be frequently positive results
present in otherwise well infants.34 Risks, harm, cost May miss cases of child abuse and potential subsequent
harm
There are insufficient data to Benefit-harm assessment The benefits of reducing unnecessary testing, sedation,
support the use of commercial radiation exposure, and false-positive results, as well
infant monitoring devices marketed as alleviating caregiver and infant anxiety, outweigh the
directly to parents for the purposes rare missed diagnostic opportunity for child abuse
of SIDS prevention.63 These monitors Intentional vagueness None
Role of patient preferences Caregiver concerns may lead to requests for CNS imaging
may be prone to false alarms, Exclusions None
produce anxiety, and disrupt sleep. Strength Weak recommendation (based on low quality of evidence)
Furthermore, these machines are Key references 3, 67
frequently used without a medical
support system and in the absence of 2B. Clinicians Should Obtain an Assessment of Social Risk Factors To Detect
specific training to respond to alarms. Child Abuse in Infants Presenting With a Lower-Risk BRUE (Grade C, Moderate
Although it is beyond the scope
Recommendation)
of this clinical practice guideline, Aggregate Evidence Quality Grade C
future research may show that home Benefits Identification of child abuse
monitoring (cardiorespiratory and/
May benefit the safety of other children in the home
or oximetry) is appropriate for some
May identify other social risk factors and needs and help
infants with higher-risk BRUE.
connect caregivers with appropriate resources (eg,
financial distress)
2. Child Abuse Risks, harm, cost Resource intensive and not always available, particularly for
2A. Clinicians Need Not Obtain smaller centers
Neuroimaging (Computed Tomography, Some social workers may have inadequate experience in child
MRI, or Ultrasonography) To Detect abuse assessment
Child Abuse in Infants Presenting With May decrease caregiver’s trust in the medical team
a Lower-Risk BRUE (Grade C, Weak
Benefit-harm assessment The benefits of identifying child abuse and identifying and
Recommendation)
addressing social needs outweigh the cost of attempting to
locate the appropriate resources or decreasing the trust in
2B. Clinicians Should Obtain an
the medical team
Assessment of Social Risk Factors To
Detect Child Abuse in Infants Presenting Intentional vagueness None
With a Lower-Risk BRUE (Grade C, Role of patient preferences Caregivers may perceive social services involvement as
Moderate Recommendation) unnecessary and intrusive
Child abuse is a common and serious Exclusions None
cause of an ALTE. Previous research Strength Moderate recommendation
has suggested that this occurs in Key reference 68
up to 10% of ALTE cohorts.3,67
Abusive head trauma is the most BRUE. Four studies reported a low to screen for abusive head trauma
common form of child maltreatment incidence (0.54%–2.5%) of abusive is extremely low and has associated
associated with an ALTE. Other forms head trauma in infants presenting to risks of sedation and radiation
of child abuse that can present as an the emergency department with an exposure.32,70
ALTE, but would not be identified ALTE.22,37,67,69 If only those patients
by radiologic evaluations, include meeting lower-risk BRUE criteria Unfortunately, the subtle
caregiver-fabricated illness (formally were included, the incidence of presentation of child abuse may lead
known as Münchausen by proxy), abusive head trauma would have to a delayed diagnosis of abuse and
smothering, and poisoning. beenconditions.67,71 Significant concerning A social and environmental for the development of epilepsy and
features for child abuse (especially assessment should evaluate the other neurologic disorders, and the
abusive head trauma) can include risk of intentional poisoning, sensitivity and positive-predictive
a developmentally inconsistent or unintentional poisoning, and value of abnormal CNS imaging for
discrepant history provided by the environmental exposure (eg, home subsequent development of epilepsy
caregiver(s), a previous ALTE, a environment), because these can was 6.7% (95% confidence interval
recent emergency service telephone be associated with the symptoms [CI]: 0.2%–32%) and 25% (95% CI:
call, vomiting, irritability, or bleeding of ALTEs in infants.75–78 In 1 study, 0.6%–81%), respectively.
from the nose or mouth.67,71 8.4% of children presenting to the The available evidence suggests
Clinicians and medical team members emergency department after an minimal utility of CNS imaging to
(eg, nurses and social workers) ALTE were found to have a clinically evaluate for neurologic disorders,
should obtain an assessment of significant, positive comprehensive including epilepsy, in lower-risk
social risk factors in infants with a toxicology screen.76 Ethanol or other patients. This situation is particularly
BRUE, including negative attributions drugs have also been associated with true for pediatric epilepsy, in which
to and unrealistic expectations of ALTEs.79 Pulmonary hemorrhage even if a patient is determined
the child, mental health problems, can be caused by environmental ultimately to have seizures/epilepsy,
domestic violence/intimate partner exposure to moldy, water-damaged there is no evidence of benefit from
violence, social service involvement, homes; it would usually present with starting therapy after the first seizure
law enforcement involvement, and hemoptysis and thus probably would compared with starting therapy
substance abuse.68 In addition, not qualify as a BRUE.80 after a second seizure in terms of
clinicians and medical team members achieving seizure remission.81–83
can help families identify and use 3. Neurology However, our recommendations
resources that may expand and 3A. Clinicians Should Not Obtain for BRUEs are not based on any
strengthen their network of social Neuroimaging (Computed Tomography, prospective studies and only on a
support. MRI, or Ultrasonography) To Detect single retrospective study. Future
Neurologic Disorders in Infants work should track both short- and
In previously described ALTE cohorts, Presenting With a Lower-Risk BRUE long-term neurologic outcomes when
abnormal physical findings were (Grade C, Moderate Recommendation) considering this issue.
associated with an increased risk of
abusive head trauma. These findings Epilepsy or an abnormality of brain 3B. Clinicians Should Not Obtain an
include bruising, subconjunctival structure can present as a lower- EEG To Detect Neurologic Disorders
hemorrhage, bleeding from the nose risk BRUE. CNS imaging is 1 method in Infants Presenting With a Lower-
or mouth, and a history of rapid head for evaluating whether underlying Risk BRUE (Grade C, Moderate
enlargement or head circumference abnormalities of brain development Recommendation)
>95th percentile.67,70–74 It is or structure might have led to Epilepsy may first present as a lower-
important to perform a careful the BRUE. The long-term risk of a risk BRUE. The long-term risk of
physical examination to identify diagnosis of neurologic disorders epilepsy ranges from 3% to 11% in
subtle findings of child abuse, ranges from 3% to 11% in historical historical cohorts of ALTE patients.2,32
including a large or full/bulging cohorts of ALTE patients.2,32 One EEG is part of the typical evaluation
anterior fontanel, scalp bruising or retrospective study in 243 ALTE for diagnosis of seizure disorders.
bogginess, oropharynx or frenula patients reported that CNS imaging However, the utility of obtaining an
damage, or skin findings such as contributed to a neurologic diagnosis EEG routinely was found to be low
bruising or petechiae, especially on in 3% to 7% of patients.4 However, in 1 study.32 In a cohort of 471 ALTE
the trunk, face, or ears. A normal the study population included patients followed both acutely and
physical examination does not rule all ALTEs, including those with a long-term for the development of
out the possibility of abusive head significant past medical history, non– epilepsy, the sensitivity and positive-
trauma. Although beyond the scope well-appearing infants, and those predictive value of an abnormal
of this guideline, it is important for with tests ordered as part of the EEG for subsequent development
the clinician to note that according emergency department evaluation. of epilepsy was 15% (95% CI:
to the available evidence, brain In a large study of ALTE patients, 2%–45%) and 33% (95% CI:
neuroimaging is probably indicated the utility of CNS imaging studies 4.3%–48%), respectively. In contrast,
in patients who qualify as higher-risk in potentially classifiable lower- another retrospective study in 243
because of concerns about abuse risk BRUE patients was found to be ALTE patients reported that EEG
resulting from abnormal history or low.32 The cohort of 471 patients was contributed to a neurologic diagnosis
physical findings.67 followed both acutely and long-term in 6% of patients.4 This study
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e16 FROM THE AMERICAN ACADEMY OF PEDIATRICS3A. Clinicians Should Not Obtain Neuroimaging (Computed Tomography, MRI, or 3C. Clinicians Should Not Prescribe
Ultrasonography) To Detect Neurologic Disorders in Infants Presenting With a Antiepileptic Medications for Potential
Lower-Risk BRUE (Grade C, Moderate Recommendation) Neurologic Disorders in Infants
Presenting With a Lower-Risk BRUE
Aggregate Evidence Quality Grade C (Grade C, Moderate Recommendation)
Benefits Reduce unnecessary testing, radiation exposure, sedation,
caregiver/infant anxiety, and costs Once epilepsy is diagnosed,
Avoid consequences of false-positive results treatment can consist of therapy
Risks, harm, cost May rarely miss diagnostic opportunity for CNS causes of with an antiepileptic medication.
BRUEs
May miss unexpected cases of abusive head trauma
In a cohort of 471 ALTE patients
Benefit-harm assessment The benefits of reducing unnecessary testing, radiation followed both acutely and long-
exposure, sedation, and false-positive results, as well as term for the development of
alleviating caregiver and infant anxiety, outweigh the rare epilepsy, most patients who
missed diagnostic opportunity for CNS cause
developed epilepsy had a second
Intentional vagueness None
Role of patient preferences Caregivers may seek reassurance from neuroimaging and event within 1 month of their
may not understand the risks from radiation and sedation initial presentation.32,87 Even if a
Exclusions None patient is determined ultimately to
Strength Moderate recommendation have seizures/epilepsy, there is no
Key references 2, 32, 81
evidence of benefit from starting
therapy after the first seizure
3B. Clinicians Should Not Obtain an EEG To Detect Neurologic Disorders in Infants compared with starting therapy
Presenting With a Lower-Risk BRUE (Grade C, Moderate Recommendation) after a second seizure in terms of
achieving seizure remission.81–83,85
Aggregate Evidence Quality Grade C
Benefits Reduce unnecessary testing, sedation, caregiver/infant anxiety,
Sudden unexpected death in epilepsy
and costs (SUDEP) has a frequency close to 1
Avoid consequences of false-positive or nonspecific results in 1000 patient-years, but the risks
Risks, harm, cost Could miss early diagnosis of seizure disorder of SUDEP are distinct from ALTEs/
Benefit-harm assessment The benefits of reducing unnecessary testing, sedation, and BRUEs and include adolescent age
false-positive results, as well as alleviating caregiver
and infant anxiety, outweigh the rare missed diagnostic
and presence of epilepsy for more
opportunity for epilepsy than 5 years. These data do not
Intentional vagueness None support prescribing an antiepileptic
Role of patient preferences Caregivers may seek reassurance from an EEG, but they may medicine for a first-time possible
not appreciate study limitations and the potential of false- seizure because of a concern for
positive results
Exclusions None
SUDEP. Thus, the evidence available
Strength Moderate recommendation for ALTEs suggests lack of benefit for
Key references 32, 84, 85 starting an antiepileptic medication
for a lower-risk BRUE. However, our
recommendations for BRUEs are
population differed significantly from no utility for routine EEG to evaluate
based on no prospective studies and
that of Bonkowsky et al32 in that for epilepsy in a lower-risk BRUE.
on only a single retrospective study.
all ALTE patients with a significant However, our recommendations for
Future work should track both
past medical history and non–well- BRUEs are based on no prospective
short- and long-term epilepsy when
appearing infants were included in studies and on only a single
considering this issue.
the analysis and that tests ordered retrospective study. Future work
in the emergency department should track both short- and long- 4. Infectious Diseases
evaluation were also included in the term epilepsy when considering this
measure of EEG yield. issue. 4A. Clinicians Should Not Obtain a
White Blood Cell Count, Blood Culture,
A diagnosis of seizure is difficult to Finally, even if a patient is or Cerebrospinal Fluid Analysis or
make from presenting symptoms determined ultimately to have Culture To Detect an Occult Bacterial
of an ALTE.30 Although EEG is seizures/epilepsy, the importance of Infection in Infants Presenting With
recommended by the American an EEG for a first-time ALTE is low, a Lower-Risk BRUE (Grade B, Strong
Academy of Neurology after a first- because there is little evidence that
Recommendation)
time nonfebrile seizure, the yield and shows a benefit from starting therapy Some studies reported that ALTEs
sensitivity of an EEG after a first-time after the first seizure compared with are the presenting complaint of
ALTE in a lower-risk child are low.86 after a second seizure in terms of an invasive infection, including
Thus, the evidence available suggests achieving seizure remission.81–83,85 bacteremia and/or meningitis
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