case based learning: alte · 12-lead ecg- normal sinus rhythm, no pavs, pvcs. normal qtc. he was...

Case based learning: ALTE

Objectives:

Medical expert

Understand definition and etiology of ALTE

Able to differentiate benign from serious causes

Understand risk factors for ALTE vs. SIDS

Collaborator

Understand proper utility of investigations

Understand indications of admission

Case

You are a Pediatrician on-call at a community hospital. The Emergency doctor calls you to

assess a 6 weeks old boy Ethan, brought to Emergency by his parents because of pale, limp

and maybe apnea. The Emergency doctor says it doesn’t sound like a seizure, because the

boy had no jerky movement. But, he doesn’t feel comfortable with babies. He would appreciate

your help. On your way to Emergency Department, you have a list of differential diagnoses

going through your mind. Also, you quickly remind yourself the questions you should ask on

history and highlights on physical exam.

<Pause for discussion>

While talking to Ethan’s parents, you gather the following history:

HPI:

It happened about 2 hours ago, when was about to fall asleep in father’s arm. Initially,

father was able to feel him breathing. Then, it seemed stopped. When he looked at Ethan,

his face was pale. He tried to wake him up. He was not responding and was limp. He

called mother for help. Mother picked Ethan up and tapped his back. He cried, turned red,

and started to move his limbs. Through the event, they didn’t see any eye deviation, lip

smacking, stiffness or jerky movement. The total duration was 30 seconds at most. After

that, he fell asleep. He was woken up by the Emergency doctor. Now, he seems back to

himself.

He was breast fed with term baby formula top up. The feed prior to the event was almost

formula. He had spit ups from time to time. Father burped him. He had no spit up at that

time.

Otherwise, he seemed normal to them. He was voiding and stooling as usual.

No sick contact.

PMHx:

He was born to 38 year old, G4P0 mother at 37 weeks. The pregnancy was conceived by

intrauterine insemination. Mother had regular antenatal care. Her OGTT test showed

borderline. She was on diet control. Other than perinatal vitamins, she didn’t take any

medication. No smoking, alcohol or drugs. Her GBS was +ve. She received multiple

doses of Pen G. Ethan was born after 24 hours of ROM. He cried immediately. No

resuscitation required. BW 3.25kg.

He was kept with mother. Nurses checked his Glucose 3 times. They were all normal. He

had mild jaundice. No phototherapy needed. He was discharged home on day 2.

He was followed by family doctor. Initially, he had significant weight loss. Then, he picked

up after formula was added. They just saw their family doctor 2 days ago. Everything was

on the right track.

Family and social history:

Father is Caucasian, mother is Asian. They were married for almost 5 years. Father has a

benign heart murmur. Mother has mild anxiety, never required medication. Other than that,

they are healthy. Paternal grandfather died of heart attack just before 50 years of age.

Maternal grandmother was just found having hypothyroidism.

Both parents are having professional jobs. They are very thankful having Ethan. There

are families and friends supporting them.

O/E:

Wt, Ht, HC all above 50%, Vitals stable. 4-limb BP normal.

Well-looking, very alert and interactive. No dysmorphic feathers. Well hydrated.

AF soft and flat. Pupils equal and reactive.

Chest clear, heart normal, no murmur, normal femoral pulses, well perfused.

Abdo soft, no tenderness, no HSM.

Normal male genitalia, no hernia.

Normal tone, strength and DTR.

Mild eczema on face and thighs.

Cardiac monitor: regular sinus rhythm, no extra beats.

<What’s your DDx? Will you order any test?>

CBC, Glu, Lytes, extended lytes -normal, urinanalysis -ve.

12-lead ECG- normal sinus rhythm, no PAVs, PVCs. Normal QTc.

<Will you admit him?>

He was admitted for observation, because mother insisted. No further events noticed. He was

about to be discharged. Mother was still quite anxious. She had the following questions for

you:

1. Does he need any other tests?

2. How to prevent this from happening again?

3. Is he at higher risk of SIDS?

4. They are thinking of buying a monitor. What’s your advice?

<How would you counsel the mother?>

DOI: 10.1542/pir.33-8-3612012;33;361Pediatrics in Review

Linda Y. Fu and Rachel Y. MoonApparent Life-Threatening Events : An Update

http://pedsinreview.aappublications.org/content/33/8/361located on the World Wide Web at:

The online version of this article, along with updated information and services, is

Pediatrics. All rights reserved. Print ISSN: 0191-9601. Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2012 by the American Academy of published, and trademarked by the American Academy of Pediatrics, 141 Northwest Pointpublication, it has been published continuously since 1979. Pediatrics in Review is owned, Pediatrics in Review is the official journal of the American Academy of Pediatrics. A monthly

by Meijian Zhao on September 26, 2012http://pedsinreview.aappublications.org/Downloaded from

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http://pedsinreview.aappublications.org/

Apparent Life-Threatening Events: An UpdateLinda Y. Fu, MD, MSc,*

Rachel Y. Moon, MD*

Author Disclosure

Drs Fu and Moon have

disclosed no financial

relationships relevant

to this article. This

commentary does not

contain a discussion of

an unapproved/

investigative use of

a commercial product/

device.

Educational Gap

In 2007, Pediatrics in Review published a review article on apparent life-threatening

events (ALTEs) and the role of home monitors. This update references the previous article

and provides an update on the topic. Most novel ALTE literature since the publication of

the review in 2007 has focused on one of four areas: identifying risk factors for ALTEs;

comparing risk factors for ALTEs and sudden infant death syndrome; determining appro-

priate diagnostic testing for infants presenting with ALTEs; and evaluating the need for

infant hospitalization after an ALTE.

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

1. Recognize a child with an apparent life-threatening event (ALTE).

2. Differentiate risk factors for ALTE versus sudden infant death syndrome.

3. Know the differential diagnosis of ALTEs.

4. Know the appropriate management of a child who has an ALTE.

What We Knew ThenDefinition

Apparent life-threatening event (ALTE) refers to a constellation of unexpected physiologicevents in an infant that are witnessed by and distressing to a caregiver. In 1986, an expertpanel sponsored by the National Institutes of Health developed the now widely accepteddefinition of ALTE as “an episode that is frightening to the observer and that is character-ized by some combination of apnea, color change, marked change in muscle tone, choking,or gagging.” The expert panel rejected an association between ALTE and sudden infantdeath syndrome (SIDS). Because ALTE is a diagnosis based on symptomatology ratherthan pathophysiology, the differential diagnosis and medical evaluation of ALTEs canbe broad.

EpidemiologyThe incidence of ALTE has been described in population-based studies as 0.6 to 2.46 per1,000 live births and 0.6% to 0.8% of all emergency visits for children younger than age1 year. These figures may underestimate the true incidence of ALTE because studiesmay miss cases in which the underlying cause is identified eventually. Events occur equallybetween boys and girls. An estimate of the percentage of ALTE cases that result in deathfrom all causes is 7.6%.

Clinical AspectsDIFFERENTIAL DIAGNOSIS. In approximately one half of

all cases diagnosed as ALTE, no apparent cause for the eventis ever found. In the other one half of the cases, a comorbidcondition is identified eventually. The three most commoncomorbid conditions (gastroesophageal reflux, seizure, andlower respiratory tract infection) account for roughly 50%of all diagnoses eventually made. There are also other lesscommon but potentially dangerous or treatable conditions

Abbreviations

ALTE: apparent life-threatening eventCBC: complete blood cellCT: computed tomographySIDS: sudden infant death syndrome

*Division of General Pediatrics and Community Health, Goldberg Center for Community Pediatric Health, Children’s National

Medical Center; George Washington University School of Medicine and Health Sciences, Washington, DC

Article respiratory

Pediatrics in Review Vol.33 No.8 August 2012 361



associated with ALTE (Table 1). Careful consideration isnecessary when attributing ALTE to gastroesophagealreflux because half of all normal infants age 0 to 3 monthsmay experience daily regurgitation.

Nonaccidental trauma should always be consideredin an infant who presents with ALTE. Because childabuse can take many forms such as inflicted head injury,poisoning, and smothering, all of which are often dif-ficult to diagnose, it is possible that some cases ofALTE with no attributable cause are actually cases ofabuse. In one study involving covert video surveillance,abuse accounted for approximately one third of all di-agnosed cases of ALTE in which initial resuscitationwas needed. (1)

EVALUATION. Infants who experience an ALTE maybe asymptomatic by the time they are brought to med-ical attention. The first task is to determine whetherthe respiratory component qualifies as true apnea ac-cording to the definition of ALTE. Shallow breathing,short episodes of central apnea lasting <30 seconds,and periodic breathing of the newborn can be normalevents if not associated with cardiac instability. Historytaking should include an assessment of severity of theevent (ie, whether the ALTE was self-resolving orwhether resolution required stimulation or resuscita-tion). It is important also to determine whether thechild experienced central cyanosis versus flushing oracrocyanosis, because the latter two color changesmay be consistent with normal changes in perfusion.Physical examination should be directed toward dis-tinguishing underlying medical conditions that canpresent as an ALTE.

HOME CARDIORESPIRATORY MONITORS. Typical homecardiorespiratory monitors, also known as apnea monitors,are designed to alert caregivers to episodes of apnea andbradycardia. Some also assess blood oxygen saturationand have event recorders. Although there is no convincingevidence that apnea monitors can prevent SIDS afterALTE, monitoring may be appropriate for two groups:(1) premature infants who are at high risk of recurrentepisodes of apnea, bradycardia, and hypoxemia, and (2) in-fants who are technology dependent, have unstable air-ways, have medical conditions with disregulated breathing,or have chronic lung disease.

What We Have Learned Since ThenMost novel ALTE literature since publication of the re-view in 2007 has focused on one of four areas: identi-fying risk factors for ALTE; comparing risk factors for

ALTE and SIDS; determining appropriate diagnostictesting for infants presenting with ALTE; and evaluat-ing the need for infant hospitalization after an ALTE.In addition, there have been articles that have reaf-firmed the commonly diagnosed conditions presentingas ALTE, but because little novel information has beenadded to this area of inquiry, we will focus on the otherfour areas.

Recently Recognized Risk Factors for ALTEsPOSTCONCEPTIONAL AGE. Infants born prematurely

(<37 weeks’ estimated gestational age) are at increasedrisk for ALTE, given their immature respiratory centers,arousal mechanisms, and airway reflexes. In a nationalsurveillance survey of all secondary and tertiary care facil-ities in the Netherlands in 2002, the percentage of pre-mature infants who experienced an ALTE (29.5%) wasover twice the percentage in the general population(13%). (2)

With an awareness of the role of central respiratorycontrol immaturity in ALTE, the issue of age-based riskmore logically focuses on an infant’s postconceptualrather than postnatal age. Lack of identification of in-fants’ postconceptional age in earlier studies may explainapparent discrepancies between earlier and more recentstudies. For instance, although several earlier studies re-vealed that older infants (age >2 months) were at higherrisk for ALTE, in a recent study of patients admitted forALTE, having a postconceptional age of <43 weeks wasassociated with a 5.2 increased relative risk of subsequentextreme events (defined as episodes of bradycardia for‡10 seconds or apnea for ‡30 seconds). (3)

Another study revealed that among infants with a post-conceptional age of <44 weeks, preterm infants and in-fants who had experienced an ALTE were at higher riskfor so-called “extreme events” than healthy term infants.(4) This effect was not apparent among infants witha postconceptional age of ‡44 weeks. Central respiratorycontrol is not completely functional even at term. Thus, onestudy revealed that postconceptional age of <48 weeksamong preterm infants and postnatal age of <1 monthamong term infants was associated with bronchiolitis-associated apnea. (5)

FIRST 2 HOURS AFTER BIRTH. Recently, researchershave recognized the risk of severe ALTE (as well as SIDS)among healthy term infants within the first 24 hours ofage. A nationwide retrospective survey in Germany re-vealed the rate of severe ALTE (requiring resuscitation)and SIDS in the first 24 hours was 2.6 per 100,000 livebirths. (6) The majority of these cases occurred during

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362 Pediatrics in Review Vol.33 No.8 August 2012



Table 1. Apparent Life-Threatening Events (ALTEs): Common Causes andPotential Discriminating Features

Causes Potential Discriminating Features

Causes Associated With Central Apnea

Central nervous system:Seizure • Loss of consciousness

• Eye deviation• Convulsion• Hypotonia or hypertonia• Micro- or macrocephaly or other dysmorphic features

Apnea of infancy/breath-holding spells • Lack of other associationsMetabolic • Family history of metabolic disorder or death in childhood

• Seizure activity• History of feeding difficulties or frequent or severe illnesses• Dysmorphic features

Cardiovascular:DysrhythmiaCongenital heart disease

• History of feeding difficulties• Diaphoresis• Central cyanosis

Infectious:MeningitisSepsisUrinary tract infection

• Fever or hypothermia• Lethargy

Medications:Drug toxicity • Lethargy

• History of medication useIntentional poisoning • Lethargy

• Delayed presentation for care• Discrepancies in the historian’s account of the ALTE• Sibling of sudden infant death syndrome (SIDS)• History of ALTE

Causes Associated With Obstructive Apnea or Mixed Central/Obstructive Apnea

Gastrointestinal:Gastroesophageal refluxAspiration

• Vomiting, coughing, choking, or gasping• Recent feeding• Milk in the mouth or nose

IntussusceptionVolvulus

• Bilious emesis• History of pulling legs to the chest during the ALTE• Bloody/mucusy stools• Lethargy after the ALTE• Abdominal distension (with volvulus)

Respiratory:Infection (especially with respiratory syncytialvirus or pertussis)

• Coryza• Coughing• Wheezing• Fever or hypothermia

Aspiration/foreign body • History of ingestion• Stridor

Airway anomaly • Stridor• History of feeding difficulties

Nonaccidental trauma:SmotheringBlunt traumaMunchausen by proxy

• History of trauma• Blood in the mouth or nose• Sibling of SIDS• History of ALTE• Delayed presentation for care

Continued

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the first 2 hours after birth. A prospective regional studyfrom France revealed a rate of ALTE and SIDS to be0.032 deaths per 1,000 live births within the first 2 hoursafter birth. (7)

Although rare, severe ALTE and SIDS among infantswithin the first few hours of birth seemed to be morecommon among primiparous mothers, during earlyskin-to-skin contact or breastfeeding, and when infantswere not being observed by health-care personnel. Mostcases were thought to be caused by obstruction of the in-fant airway. Thus, although early skin-to-skin contact formaternal-infant bonding and early establishment ofbreastfeeding are undoubtedly important, it would beprudent if these practices occurred with constant surveil-lance (recognizing the logistic difficulties associated withthis suggestion) or at least frequent checks by health-carepersonnel within the first 2 hours after birth when boththe mother and infant can be expected to be fatigued. Af-ter testing for effectiveness for preventing perinatal ALTEand SIDS, wireless cardiorespiratory monitors may beuseful to health-care personnel for providing surveillancein the future.

Comparison of ALTE to SIDSAs stated by the American Academy of Pediatrics TaskForce on SIDS, there is no evidence that an ALTE isa precursor to SIDS. This lack of association is evidencedby the fact that the incidence of SIDS has decreased sincethe 1994 Back to Sleep Campaign, whereas the incidenceof ALTE has not. Also, most risk factors for ALTE andSIDS are different. For instance, approximately half ofALTEs occur during wakefulness, whereas the majorityof SIDS cases occur during sleep. In fact, extreme apneicand bradycardic events are less common during the earlymorning hours when SIDS tends to occur and morecommon among Asians who are at lower risk for SIDS.In addition, the age of mothers of infants who haveALTE follows the distribution of the normal population,whereas the distribution of mothers whose infants die of

SIDS is skewed toward a younger age. ALTEs occurequally between boys and girls, whereas boys succumbto SIDS more frequently than girls.

Although ALTE is not a precursor to SIDS, the twoentities may share similar risk factors, which could explainwhy 0% to 7% of SIDS cases are preceded by an ALTE.The one common risk factor for both ALTE and SIDS ismaternal smoking. In one study, 33.3% of infants withALTE who subsequently died of SIDS had the dual riskfactors of prone sleep position and late prenatal smoke ex-posure, compared with 13.3% of ALTE survivors. (8) Aseparate study of polysomnograms revealed that infantswho had experienced an ALTE and who had nonsmok-ing mothers had fewer total arousals, cortical arousals,and subcortical activations than normal controls, but thattheir spontaneous arousals were altered in patterns thatdiffered from future SIDS victims. (9) However, infantswho had ALTE whose mothers smoked had arousal andrespiratory characteristics similar to future SIDS victims.These two studies suggest that there may be a minor sub-population of infants who have experienced an ALTEwho are at higher risk of SIDS and that at least part ofthis risk may be conferred by maternal smoking.

Diagnostic TestingA recent review of 36 children’s hospitals across theUnited States revealed that the most common laboratorystudies ordered after an ALTE episode were completeblood cell (CBC) count (70%) and electrolytes (65%).(10) A chest radiograph was ordered in 69% of patients,26% had upper gastrointestinal fluoroscopy or swallowtesting, and 36% had electrocardiography performed.There was large interhospital variability for all aspectsof care involving ALTE, including costs, diagnostic tests,and medications.

In 2009, the Dutch Pediatric Association becamethe first national pediatric association to advocate useof an evidence-based consensus pathway for the diag-nosis, management, and follow-up of children who have

Table 1. (Continued)

Causes Potential Discriminating Features

• Discrepancies in the historian’s account of the ALTE• Vomiting/irritability• High severity ALTE or emergency medical services

involvementAccidental smothering • ALTE occurred while infant was sleeping

• Infant was in the prone position• Infant had soft objects (eg, pillows or blankets)

covering/near face

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experienced an idiopathic ALTE. (11) The pathway rec-ommends a minimum initial diagnostic panel for ALTEthat includes the following: CBC count with differential,C-reactive protein, serum glucose level, arterial blood gasdeterminations, urinalysis, electrocardiography, and as-sessments for Bordetella pertussis and respiratory syncytialvirus in season (with other diagnostic tests performed atthe clinician’s discretion). There is solid evidence for thebenefit of including these tests in the initial evaluation ofa child presenting with ALTE.

The minimum diagnostic panel suggested by theDutch Pediatric Association is less inclusive than the oftencited algorithm published previously by McGovern andSmith in 2004 (12) based on a systematic review of studiesdetailing the final diagnoses of ALTE cases. In addition tothe tests advocated in the Dutch pathway, McGovern andSmith (12) also include in the initial evaluation serummetabolic studies, urine toxicology screening, investiga-tions for gastroesophageal reflux, EEG, and head imag-ing. In the next few paragraphs, we will review therecent evidence for and against inclusion of these otherstudies in the routine initial investigations for idiopathicALTE, keeping in mind that screening tests ideallyshould be sensitive, relatively specific, not too expensive,relatively easy to obtain, and not excessively burdensomefor the patient.

ELECTROENCEPHALOGRAPHY. McGovern and Smith(12) recommended inclusion of EEG in initial investiga-tions based on the fact that, in their review, seizures ac-counted for 11% of the total final diagnoses. However,only two of seven studies in their review revealed thatthe diagnosis of epilepsy was made by EEG. It is possiblethen that the diagnosis in other studies was made fromother evidence, such as parental report of the episode be-ing consistent with seizure, underlying serum chemistryanomaly, or abnormal brain imaging.

In a 5-year study by Bonkowsky et al in 2008 (13),EEG had a sensitivity of only 15% for diagnosing epilepsy.Of the 3.6% of infants in that study who presented withALTE and developed chronic epilepsy, 71% had a recur-rent ALTE event within 1 month, and 47% were diag-nosed as having seizures within 1 week of the initialevent. Given that EEG is difficult to obtain in the emer-gency department setting and has a low sensitivity fordiagnosing chronic epilepsy, as well as the fact that mostpatients who have epilepsy return with a second episode,we suggest that EEG be reserved for those with recurrentALTE.

NEUROLOGIC IMAGING. In addition to EEG, neuro-logic imaging, including cranial computed tomography

(CT), MRI, and ultrasonography can be used to help di-agnose chronic epilepsy by demonstrating underlying an-atomic anomalies. Neurologic imaging also can identifypatients who have experienced abusive head trauma. Inthe study by Bonkowsky et al (13), all neurologic imagingmodalities together had a sensitivity for predictingchronic epilepsy of only 6.7%.

The most common cranial imaging study ordered forALTE workup is head CT. Head CT is ordered morecommonly than head ultrasonography and MRI com-bined. Head CT may be abnormal in 63% to 70% of casesof closed head injury. This fact is important becauseabusive head trauma may be missed in the emergencydepartment; approximately one half of the cases wereundetected in one study. By using Markov models, re-searchers have found that ordering head CT for allasymptomatic infants with history of ALTE actually savesmoney from a medical payer perspective. (14) Neverthe-less, onlyw1% to 3% of all cases of ALTE are due to abu-sive head trauma, meaning that many infants would beirradiated unnecessarily if all infants presenting withALTE were to undergo head CT.

Instead of compulsive head CTs for all infants present-ing with ALTE, we feel that neurologic imaging shouldbe reserved for cases suspicious for abuse. In two separatestudies, a documented discrepancy in the history of theALTE (eg, history is confusing, varies among caregivers,or changes over the course of the evaluation) was highlypredictive of physical abuse. These studies revealed thata delay in seeking medical care in one study and vomiting,irritability, or a call to 911 in the other, also were associ-ated with abusive head trauma. (15)(16)

Given the high levels of radiation associated with headCT, we suggest having multiple emergency departmentpersonnel use a checklist (Table 2) to take the historyfrom the caregiver more than once, looking for inconsis-tencies and for other potential markers of abuse, and re-serving head CT for suspicious cases. In suspected casesof physical abuse, retinal examinations, which may de-tect 33% to 60% of head trauma, and skeletal surveys,which may detect 14% of physical abuse, also shouldbe obtained. Covert video surveillance while the infantis hospitalized to detect the caretaker smothering orshaking the infant also should be considered in suchcircumstances.

SERUM METABOLIC STUDIES. The following bloodchemistry concentrations are included in the McGovernand Smith (12) initial minimum screening: sodium, po-tassium, urea, calcium, magnesium, ammonia, lactate,and pyruvate. Although the results from a basic serum

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metabolic panel are not likely to reveal a definitive causeof the ALTE, they may suggest a cause. For instance,studies have identified rare cases of ALTE due to hypocal-cemia and hypomagnesemia. Other electrolyte disturban-ces conceivably could present as ALTE, such as hypo- orhypernatremia leading to seizures and hypo- or hyperka-lemia leading to cardiac arrhythmias.

Metabolic disorders, including organic acidemias, ureacycle disorders, fatty acid oxidation disorders, and mito-chondrial disorders, cause w2% to 5% of all cases ofALTE. Although they account for a minority of eventualALTE diagnoses, ALTE can be a classic initial presenta-tion for an infant who has a metabolic disorder. If not rec-ognized and treated promptly, some metabolic disorderscan progress and lead to long-term sequelae. Because se-rum chemistry tests are relatively inexpensive, easy to ob-tain, and may be the only means of diagnosing somedisorders for which early treatment is important, weadvocate for their inclusion in the initial evaluation ofALTE.

URINE TOXICOLOGY SCREENING. Including urine tox-icology screening in the initial evaluation of ALTE canuncover cases of intentional and unintentional poisoning.In a prospective study of children younger than age2 years presenting with an ALTE, of the 274 childrenwho had a toxicology screen performed, 8.4% were pos-itive for a medication that could have caused apnea. (17)Notably, 4.7% of infants screened positive for over-the-counter cough and cold preparations, some of which con-tain ingredients that may cause apnea in infants. Coughand cold medications are not recommended for childrenunder age 2 years, and none of the parents in the studyadmitted to having administered any to their infants. Forthese reasons and because the test is relatively inexpensiveand easy to obtain, we suggest including urine toxicologyscreening in the initial set of tests for ALTE.

INVESTIGATIONS FOR GASTROINTESTINAL REFLUX. Ap-proximately one in four infants admitted with ALTEundergoes an upper gastrointestinal fluoroscopy or swal-low test. Although these tests are useful for demonstrat-ing anatomic anomalies as a cause for ALTE, they are lessuseful for proving gastroesophageal reflux as the causebecause daily regurgitation is typical for many normal in-fants. A better test for demonstrating a causal link be-tween gastrointestinal reflux and ALTE is esophagealpH sampling via a pH probe, correlating the probe find-ings with episodes of apnea or hypoxemia documentedon concurrent cardiorespiratory monitoring. However,pH probe results that demonstrate acid reflux not as-sociated with respiratory compromise do not allow for

Table 2. Example: StandardizedChecklist for Obtaining ALTEHistory

Who observed the episode? Try to obtain history directlyfrom the observer, by phone if necessary.

When did the episode occur?What was the infant doing right before the episode?If she was asleep, where was she and in what position?

Did the infant fall or experience any other trauma?Does the infant currently have a runny nose, cough,vomiting, diarrhea, or fever?

How was the infant acting on the day the episodeoccurred?

How did the infant look during the episode?Did she gasp, choke, gag, or cough?Did her body change color and if so what part?Did she vomit?Did she become weak, floppy, limp, stiff, or startshaking?

Did she lose consciousness?Did the observer notice any unusual eye rolling?Did the observer notice any blood, milk, or stomachcontents in her mouth or nose during or right afterthe episode?

How long do you think the episode lasted? If theobserver is unsure, ask him to describe or act outexactly the occurrence of events and what he wasdoing from start to finish.

Did the episode stop on its own or did someone dosomething to stop it?If someone intervened: What did that person do?Were emergency medical services involved?

How has the infant been acting since the episodeoccurred?

Please name any prescription or over-the-countermedication or herbal remedies that the infant receivedwithin 24 h before the episode.For breastfeeding mothers: please name anyprescription or over-the-counter medication or herbalremedies that the infant’s mother took within 24 hbefore the episode.

Has the infant ever experienced a similar episode in thepast and, if so, what was done to evaluate herafterward?

Does the infant have any medical problems orconditions?

When was the infant born: on time (at 40 wk ofpregnancy), early, or late?

Has anyone in the infant’s family ever experienceda similar episode or died of sudden infant deathsyndrome, also called SIDS?

Has anyone in the infant’s family been diagnosed witha genetic, metabolic, cardiac, or neurological conditionor died in childhood of unknown causes?

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decisive attribution of the ALTE to reflux. In addition,the test is fairly uncomfortable for patients and not inex-pensive. Therefore, we suggest gastrointestinal refluxtesting be included in an ALTE evaluation only if the in-fant reportedly has frequent gastrointestinal reflux, theALTE was immediately preceded by a feeding, or gastriccontents were noted in the infant’s mouth or nose by thecaregiver during the episode.

HOSPITAL OBSERVATION VERSUS DISCHARGE FROM

HOSPITAL. Admitting an infant after an ALTE can fa-cilitate diagnostic testing for an underlying cause and al-low for prompt medical intervention if the need arises.However, typical hospital charges for an ALTE admis-sion were $15,567 in one study, and it is unclearwhether all infants who experience an ALTE need tobe admitted. (10) Thus far, there has not been anylarge-scale prospective trial of a predictive model to de-termine which infants need to be admitted after anALTE due to a high risk of experiencing a subsequentlife-threatening event requiring immediate medical in-tervention. Also, there are no data as to current admis-sion rates.

The average length of stay for infants admitted forALTE in the United States is 4.4 days, with wide varia-tion among hospitals. In a retrospective study of 625 in-fants admitted for ALTE, 13.6% had a subsequentextreme cardiorespiratory event, 85% of which occurredwithin the first 24 hours of hospitalization. (3) Most ex-treme events were associated with an eventual diagnosisof respiratory tract infection and occurred on averagewithin 4 days of initial presentation. Risk factors for hav-ing an extreme event were prematurity, postconceptionalage <43 weeks, and displaying symptoms of upper respi-ratory tract infection.

In a prospective case series in which all 66 infants wereadmitted for ALTE for at least 24 hours, 12% had recur-rent episodes within 24 hours, 9% had episodes requiringmoderate stimulation, and 3% required resuscitationmeasures. (18) Approximately one half of the patients re-quiring medical intervention were born prematurely. Inanother prospective study of 59 infants, age <1 monthand having had a previous ALTE conferred higher riskof requiring acute medical attention. (19) Based on thesestudies, we believe that the majority of infants who haveexperienced an ALTE should be admitted for a minimumof 23 hours of observation, with continuous cardiorespi-ratory monitoring and, ideally, continuous measurementof pulse oximetry with event recording.

If the event is an infant’s first ALTE; he was not bornprematurely; he has no significant medical history; he is

well-appearing with stable vital signs at the time of eval-uation; the episode was brief, nonsevere, and self-resolving;and if there is a probable cause that is nonprogres-sive (such as gastroesophageal reflux), it may be reason-able to discharge the infant without 23 hours ofobservation.

Regardless of whether an infant is admitted after anALTE, caretakers should be educated about techniquesto prevent and treat further episodes. Specifically, care-takers should be told not to shake their infants duringan ALTE because shaking may cause physical harm. Ap-proximately one in three parents shook their infants tostimulate them during an ALTE, according to a nationalDutch survey. (2) Resources for infant basic life supportcourses should be given to caretakers. In addition, itis important to ensure follow-up for the infant with ahealth-care practitioner soon after discharge becausew10% of ALTEs are recurrent.

References1. Southall DP, Plunkett MC, Banks MW, Falkov AF, Samuels MP.Covert video recordings of life-threatening child abuse: lessons forchild protection. Pediatrics. 1997;100(5):735–7602. Semmekrot BA, van Sleuwen BE, Engelberts AC, et al. Surveil-lance study of apparent life-threatening events (ALTE) in theNetherlands. Eur J Pediatr. 2010;169(2):229–236

Summary

• Based on strong research evidence, the most commoncauses of apparent life-threatening events (ALTEs) aregastroesophageal reflux, lower respiratory tractinfection, and seizure. (2)(12)(13)(20)

• The minimum initial diagnostic panel for ALTE shouldinclude complete blood cell (CBC) count withdifferential; blood levels of C-reactive protein,glucose, sodium, potassium, urea, calcium,magnesium, ammonia, lactate, and pyruvate; arterialblood gas determination, urinalysis, and toxicologyscreen; electrocardiography; and assessments forBordetella pertussis and respiratory syncytial virus inseason. (11)(12)(17)

• Other testing should be done based on the infant’sclinical presentation and clinician’s degree of suspicion.

• Most infants should be hospitalized forcardiorespiratory monitoring for 23 hours after anALTE. (3)(18)(19)

• There is strong evidence that newborns are at higherrisk of ALTE and sudden infant death syndrome (SIDS)within the first 24 hours after birth and thereforeshould be frequently monitored as much as possiblewhile room sharing with their mothers. (6)(7)

• Evidence suggests that maternal smoking may placean infant for higher risk of SIDS after an ALTE. (8)(9)

respiratory alte




3. Al-Kindy HA, Gelinas JF, Hatzakis G, Cote A. Risk factors forextreme events in infants hospitalized for apparent life-threateningevents. J Pediatr. 2009;154(3):332–3374. Hoppenbrouwers T, Hodgman JE, Ramanathan A, Dorey F.Extreme and conventional cardiorespiratory events and epidemio-logic risk factors for SIDS. J Pediatr. 2008;152(5):636–6415. Willwerth BM, Harper MB, Greenes DS. Identifying hospital-ized infants who have bronchiolitis and are at high risk for apnea.Ann Emerg Med. 2006;48(4):441–4476. Poets A, Steinfeldt R, Poets CF. Sudden deaths and severeapparent life-threatening events in term infants within 24 hours ofbirth. Pediatrics. 2011;127(4):e869–e8737. Dageville C, Pignol J, De Smet S. Very early neonatal apparentlife-threatening events and sudden unexpected deaths: incidenceand risk factors. Acta Paediatr. 2008;97(7):866–8698. Edner A, Wennborg M, Alm B, Lagercrantz H. Why do ALTEinfants not die in SIDS? Acta Paediatr. 2007;96(2):191–1949. Franco P, Montemitro E, Scaillet S, et al. Fewer spontaneousarousals in infants with apparent life-threatening event. Sleep. 2011;34(6):733–74310. Tieder JS, Cowan CA, Garrison MM, Christakis DA. Variationin inpatient resource utilization and management of apparent life-threatening events. J Pediatr. 2008;152(5):629–63511. Wijers MM, Semmekrot BA, de Beer HJ, Engelberts AC.Multidisciplinary guidelines for ‘Apparent life threatening event’(ALTE). Ned Tijdschr Geneeskd. 2009;153:A59012. McGovern MC, Smith MB. Causes of apparent life threateningevents in infants: a systematic review. Arch Dis Child. 2004;89(11):1043–1048

13. Bonkowsky JL, Guenther E, Filloux FM, Srivastava R. Death,child abuse, and adverse neurological outcome of infants after anapparent life-threatening event. Pediatrics. 2008;122(1):125–13114. Campbell KA, Berger RP, Ettaro L, Roberts MS. Cost-effectiveness of head computed tomography in infants withpossible inflicted traumatic brain injury. Pediatrics. 2007;120(2):295–30415. Vellody K, Freeto JP, Gage SL, Collins N, Gershan WM. Cluesthat aid in the diagnosis of nonaccidental trauma presenting as anapparent life-threatening event. Clin Pediatr (Phila). 2008;47(9):912–91816. Guenther E, Powers A, Srivastava R, Bonkowsky JL. Abusivehead trauma in children presenting with an apparent life-threateningevent. J Pediatr. 2010;157(5):821–82517. Pitetti RD, Whitman E, Zaylor A. Accidental and nonacciden-tal poisonings as a cause of apparent life-threatening events ininfants. Pediatrics. 2008;122(2):e359–e36218. Santiago-BurruchagaM, Sánchez-Etxaniz J, Benito-Fernández J,et al. Assessment and management of infants with apparent life-threatening events in the paediatric emergency department. Eur JEmerg Med. 2008;15(4):203–20819. Claudius I, Keens T. Do all infants with apparent life-threatening events need to be admitted? Pediatrics. 2007;119(4):679–68320. Kahn A; European Society for the Study and Prevention ofInfant Death. Recommended clinical evaluation of infants with anapparent life-threatening event. Consensus document of theEuropean Society for the Study and Prevention of Infant Death,2003. Eur J Pediatr. 2004;163(2):108–115

PIR QuizThis quiz is available online at http://www.pedsinreview.aappublications.org. Note: Since January 2012, learners cantake Pediatrics in Review quizzes and claim credit online only. No paper answer form will be printed in the journal.

New Minimum Performance Level RequirementsPer the 2010 revision of the American Medical Association (AMA) Physician’s Recognition Award (PRA) and creditsystem, a minimum performance level must be established on enduring material and journal-based CME activities thatare certified for AMA PRA Category 1 CreditTM. In order to successfully complete 2012 Pediatrics in Review articles forAMA PRA Category 1 CreditTM, learners must demonstrate a minimum performance level of 60% or higher on thisassessment, which measures achievement of the educational purpose and/or objectives of this activity.

Starting with the 2012 issues of Pediatrics in Review, AMA PRA Category 1 CreditTM may be claimed only if 60% ormore of the questions are answered correctly. If you score less than 60% on the assessment, you will be givenadditional opportunities to answer questions until an overall 60% or greater score is achieved.

respiratory alte




1. A previously healthy 1-month-old boy has had a runny nose and worsening cough for 2 days. On the morningof the third day of his illness, he briefly stops breathing and turns pale and motionless. He responds to gentlestimulation and begins breathing again. His frightened mother calls 911, and he is taken immediately to theemergency department (ED) by ambulance. Given the history, you suspect his apnea is most likely caused by

A. A respiratory syncytial virus (RSV) infection.B. A seizure.C. An organic acid disorder.D. Dysrhythmia.E. Intentional poisoning.

2. A previously healthy 1-month-old boy has an episode of sudden choking and gagging that frightens his motherand grandmother. His face briefly turns red. He does spit up occasionally, but such an event has never occurredbefore. In the ED, he appears well, and a thorough examination is normal. He is admitted for 23 hours. No morespells occur. Recommended routine screening is unremarkable. His apparent life-threatening event (ALTE) ismost likely explained by

A. Gastroesophageal reflux.B. Intracranial hemorrhage.C. Pertussis.D. Seizure disorder.E. Urea cycle disorder.

3. A previously healthy 1-month-old boy is brought to the ED the morning after having had three bouts ofchoking and gagging the previous evening, during which his face and body turned dusky. His motherstates he does spit up occasionally, but such an event has never occurred before. However, the details of herhistory vary from those of her boyfriend and the grandmother. The child appears lethargic, but carefulexamination produces no other abnormal findings. He is admitted to the hospital. The explanation for the ALTEis most likely to be provided by

A. A cardiac event monitor.B. A computed tomography (CT) scan.C. An electroencephalogram.D. An esophageal pH probe.E. Organic acid screening.

4. A previously healthy 1-month-old boy has an event of floppiness and cyanosis that frightens his mother andgrandmother. He spits up occasionally, but such an event has never occurred before. In the ED, he appearslethargic and pale. Arterial blood gases reveal a mixed acidosis. Your diagnosis is an extreme ALTE. A carefulexamination produces no other abnormal physical findings. He is admitted to the hospital and graduallyrecovers fully. All other recommended routine screening tests and a CT scan produce normal results. Which oneof the following most elevates his risk for subsequent sudden infant death syndrome (SIDS)?

A. He was delivered at 44 weeks’ postconception.B. His mother is Asian.C. His mother just turned 30.D. His mother smoked cigarettes throughout the pregnancy.E. The boy sleeps on his side.

5. A 1-month-old boy has a brief event of choking and gagging that frightens his mother and grandmother. In theED, he appears well and a thorough examination is normal. No more spells occur. Given the circumstances, afterreassuring the mother and grandmother, you would be most comfortable in discharging him from the hospitaldirectly if his only risk factor for having another spell is that

A. A nasal swab is positive for RSV.B. He spits up a small amount of formula several times a day.C. He was delivered at 32 weeks’ postconception.D. The grandmother recalls one previous similar but milder episode a week ago.E. The mother smoked cigarettes throughout the pregnancy.

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DOI: 10.1542/pir.33-8-3612012;33;361Pediatrics in Review

Linda Y. Fu and Rachel Y. MoonApparent Life-Threatening Events : An Update

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ORIGINAL ARTICLE

Causes of apparent life threatening events in infants: asystematic reviewM C McGovern, M B H Smith. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

See end of article forauthors’ affiliations. . . . . . . . . . . . . . . . . . . . . . .

Correspondence to:Dr M B H Smith, ConsultantPaediatrician, Departmentof Paediatrics, CraigavonArea Hospital, LurganRoad, Portadown BT635QQ, Co. Armagh,Northern Ireland, UK;[email protected]

Accepted19 February 2004. . . . . . . . . . . . . . . . . . . . . . .

Arch Dis Child 2004;89:1043–1048. doi: 10.1136/adc.2003.031740

Aims: To determine the most likely diagnoses when infants first present with an apparent life threateningevent (ALTE).Methods: Medline (1966–2002), Embase (1980–2002), and Cinahl (1982–2002) were searched.Primary authors and content experts were contacted to identify further studies. Bibliographies from studies,reviews, and textbooks were searched. Foreign language studies were translated. Articles were included ifthe ALTE was clearly defined and if the evaluation recorded was from the initial contact. Case reports andstudies focusing on single conditions or non-clinical data were excluded.Results: From an initial 2912 papers, eight studies involving 643 infants (aged 0–13 months) wereincluded. All studies were non-randomised and methodological quality varied. All diagnoses were madeafter evaluation in hospital but investigation protocols varied widely. There were 728 diagnoses assignedoverall. Some infants had multiple diagnoses. The most common diagnoses were gastro-oesophagealreflux (n = 227), seizure (n = 83), lower respiratory tract infection (n =58), and ‘‘unknown’’ (n = 169). Fivedeaths were noted in total.Conclusions: There is a wide range of diagnoses reported after evaluation of an ALTE. Differingmanagement protocols contributed to variations in the frequency of the diagnoses. The development andvalidation of an evidence based management plan may contribute to the care of this common condition.

An apparent life threatening event (ALTE) was definedin 1986 by the National Institutes of Health ConsensusDevelopment Conference on Infantile Apnoea and

Home Monitoring as ‘‘an episode that is frightening to theobserver and that is characterised by some combination ofapnoea (central or occasionally obstructive), colour change(usually cyanotic or pallid but occasionally erythematous orplethoric), marked change in muscle tone (usually markedlimpness), choking or gagging’’.1 This new definition replacedexisting terms such as ‘‘near-miss sudden infant deathsyndrome’’ or ‘‘aborted cot-death’’ which are potentiallymisleading as they imply a close association with suddeninfant death syndrome (SIDS). Although the relationbetween ALTEs and SIDS has still not been firmly estab-lished, it is likely there is only a small overlap between thetwo populations.It has been our experience that infants who present to

the clinician because of an ALTE, particularly those whosubsequently appear well, are a challenging group to manageas it can be difficult to decide on an appropriate investigationplan. The first step in the development of an evidence basedmanagement algorithm would be to review the diagnosesreported after evaluation of ALTEs but, to our knowledge,there are no systematic reviews that have looked critically atthis in unselected infants.The aim of this systematic review is therefore to determine

the diagnoses reported after the first evaluation of an ALTE ininfants.

METHODSData sources and search strategyThe following question was structured to address the clinicalquery: ‘‘In infants, presenting with an ALTE, what is thefrequency of underlying disorders?’’. We searched for studiesthat considered a range of diagnoses in infants presentingdirectly to an emergency department or general paediatricward after an ALTE. A search was performed of the databases

Cinahl (1982–2002), Embase (1980–2002), Medline (1966–2002) in September 2000 and November 2002. No restrictionswere made on language or on the type of article to beincluded. In addition, reference lists were searched andcontact was made with experts in the field.

Study selection (inclusion and exclusion criteria)There were three stages in the selection process. Firstly, thetitles, abstracts, and descriptor terms of all the citations wereinspected for relevance by one author (MCMcG). Articleswere selected for inclusion at the first stage if they appearedto address the clinical question. Where there was uncertaintythe full article was included. Secondly, articles were assessedfor inclusion independently by both authors after evaluationof the full text and according to the following predeterminedcriteria. Articles were included if a range of diagnoses wasreported in a group of infants with ALTE and there was aclear definition of ALTE in the text. Articles were excluded ifthe study focused on physiological data or polygraphicstudies. Thirdly, articles were selected for the final summaryif the investigations reported were the first undertaken and ifall presenting infants were studied. Any disagreements wereresolved by consensus. If data in papers from the same centrewere noted to overlap, the most comprehensive study wasselected.2 3

Data extraction and synthesisOne author (MCMcG) extracted data. The primary outcomeof interest was the final diagnosis assigned but details ofincidence, investigation plans, follow up, recurrence, anddeaths were also noted. Individual studies were reportedseparately and a narrative synthesis of data was performed.

RESULTSStudy selectionWe identified 2912 citations: 2882 electronically, 29 fromreference lists, and one after personal contact with experts.3

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The selection process identified eight studies, involving 643infants, in which a range of differential diagnoses wasdescribed in a group of infants undergoing a first evaluationof ALTE. Agreement between reviewers was good (kappa0.714).

Study qualityTable 1 presents study characteristics. All studies were non-randomised, descriptive studies.

Investigation plansAll diagnoses were made after evaluation in hospital. Therange of investigations in each study varied and in six aninvestigation protocol was described (table 2).

Incidence of ALTEThe incidence of ALTE was described in four studies as0.620.8% of all emergency visits of those under 1 year,5 6 2.27%of hospitalised children,7 and 0.6/1000 live born infants.2

Final diagnosesTable 3 presents final diagnoses. In seven studies each infantwas assigned a definitive diagnosis or in some cases multiplediagnoses after an ALTE. In one study some infants presentedmore than once to the emergency department and thediagnosis made after each episode is recorded.6 There were728 diagnoses assigned in total with 50 different diagnosesrecorded. The commonest diagnoses made were gastro-oesophageal reflux disease (GORD), lower respiratory tractinfection (LRTI), and seizure.

Table 1 Characteristics of included studies

First author, country Centre, dates of episodes No.Definition of target populationExclusions

Inv.proto. Participants

A Davies (2002),England5

ED, children’s hospital,1996–97 (prospective)

65 1986 consensus definitionExclusions: infants .6 mth with febrile convulsion.

Yes age 0–12 mth, median7 weeks, 15% SIDS inrelative, 15%,34 weeks preterm

B Gray (1999),England6

ED, children’s hospital,1993 (retrospective)

130 Episode with one or more of the following: apnoea,colour change, choking, abnormal limb movements,causing observer to seek medical help. 130 infantshad 163 ALTE episodes requiring admission.Exclusions: infants .6 mth with febrile convulsion.

No age 0–12 mth, median8 weeks, 3.1% SIDS inclose family

C Kurz (1997),Austria2

Paediatric dept, universityhospital (prospective)

60 Episode of sudden, unexpected pallor or cyanosis withlifelessness, experienced by parents as mortal threat.No exclusions.

Yes age 1–45 weeks,median 16 weeks, 22%preterm

D Laisne (1989),France7

Paediatric dept, generalhospital, 1985–87(retrospective)

100 Episode of sudden, unexplained apnoea with cyanosisand/or pallor and hypotonia leading to loss ofconsciousness and often prompting carers to stimulatethe infant.No exclusions.

Yes mean 13 weeks, 90%,6 mth

E Sheikh (2000),USA10

ED, children’s hospital,1993–97 (retrospective)

74 Episode of prolonged apnoea, hypotonia andpallor or cyanosis in first year of life.No exclusions.

No age 0–12 mth, mean7 weeks, 0% preterm

F Tal (1999), Israel8 Paediatric ward, generalhospital, 1993–95(retrospective)

65 1986 consensus definition.No exclusions.

Yes age 1–6 mth

G Tsukada (1993),Japan11

Paediatric ward, generalhospital, 1986–91(retrospective)

19 1986 consensus definition.No exclusions.

Yes age 23 days–13 mth,mean 19 weeks

H V-Wauters (1991),Belgium9

ED, children’s hospital,1984–86 (retrospective)

130 Episode of prolonged apnoea, hypotonia, and cyanosisor pallor.No exclusions.

Yes age 2–36 weeks

ED, emergency department.Prospective, prospective identification of patients.Retrospective, retrospective case note review.Inv. proto., investigation protocol.

Table 2 Baseline investigations for all infants in six studies with protocols

A C D F G H A C D F G H

Basic blood tests Metabolic work upFBC, U+E, glucose + + + + + + Lactate, ammonia + 2 2 2 2 2

Calcium, magnesium 2 + + + + + Serum amino acids + 2 2 2 2 +Liver function tests 2 + 2 + 2 2 Urine organic acids + 2 2 2 2 +Blood gas or bicarbonate + + 2 + + + Urine reducing substances + 2 2 2 2 2

Thyroid hormones 2 2 2 2 2 + CardiologyCPK 2 + 2 2 2 2 ECG + + + + + +Infection screen 24 hour tape 2 2 * 2 2 2

Blood culture 2 2 2 2 2 2 Echocardiography 2 2 2 2 + 2

Urinalysis or culture + + + 2 2 2 OtherChest x ray + + + 2 + + Toxicology screen + 2 2 2 2 +If secretions present: Electroencephalogram (EEG) 2 2 2 + + +Pertussis swab + 2 2 2 2 2 Polysomnograph 2 + * 2 2 +Virology tests + 2 2 2 2 2 ENT consultation 2 2 2 2 2 +Bacteriological tests 2 2 2 2 2 2 Milk scan or barium swallow or pH studies + 2 * 2 + 2

*Performed in second year of study.CPK, creatinine phosphokinase.Note: all studies performed additional investigations in selected infants as clinically indicated.

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Table

3Fina

ldiagn

oses

Firstautho

rGIT

Respiratory

CNS

CVS

ENT

Other

Unk

nown

Davies,

n=65

GORD

17(26%)

GE1(2%)

Pertussis6(9%)

Other

LRTI

6(9%)

Seizures

5(8%)

Febrile

seizure1(2%)

Hyp

ocalcaem

icseizure1(2%)

Braintumou

r1(2%)

PDA

1(2%)

Atrialtachycardia

1(2%)

Laryng

omalacia

1(2%)

UTI

5(8%)

Factitiou

sillne

ss2(3%)

Opiates

1(3%)

Develop

men

talde

lay1(3%)

15(23%)

Gray,

n=130*

No.

ofep

isod

es=163

GORD

30(18%)

GE4(2%)

LRTI

15(9%)

Pertussis9(6%)

URTI7

(4%)

Asthm

a2(1%)

Seizures

40(25%)

Febrile

seizure

20(12%)

Hea

dinjury

2(1%)

0Su

bglotticsten

osis1(0.5%)

Cho

king

8(5%)

Normal

4(2%)

Unspe

cifie

dinfection3(2%)

UTI

2(1%)

Vom

it2(1%)

Feed

ingprob

lems2(1%)

Develop

men

tde

lay1(0.5%)

Vaccina

tionreactio

n1(0.5%)

21(13%)

Kurz,

n=60*

GORD

18(30%)

GE2(3%)

Strang

ulated

hernia

1(2%)

URTI1

1(18%)

RSV6(10%)

Aspiration

pneumon

ia2(3%)

Pertussis1(2%)

Seizures

4(7%)

Hyd

roceph

alus

2(3%)

Enceph

alitis1(2%)

IVH

1(2%)

Onidine

’ssynd

rome1(2%)

Cen

tral

apno

easynd

rome12(20%)

Werdn

igHoffm

an1(2%)

Fibroe

lastosis1(1%)

Cardiom

yopa

thy1(1%)

Oroph

arynge

alstab

ility

onbron

choscopy

2(3%)

Develop

men

tde

ficit3(5%)

Flop

pyinfant

1(2%)

Hyp

oglycaem

ia1(2%)

Hyp

ocalcaem

ia1(2%)

Carnitin

ede

f.2(3%)

Organ

icacidop

athy

1(2%)

UTI

1(2%)

5(8%)

Laisne

,n=100*

GORD

66(66%)

0Unspe

cifie

d5(5%)

0Unspe

cifie

d6(6%)

Vag

alhype

rrea

ctivity

13(13%)

Brea

thho

lding8(8%)

Toxins

4(4%)

Metab

olic

3(3%)

Infectious

3(3%)

9(9%)

Sheikh,n=74

GORD

49(66%)

RSV7(9%)

Pneumon

ia1(1%)

Seizure3(4%)

Hyp

oplastic

leftventricle1(1%)

ASD

+VSD

1(1%)

0Aspiration1(1%)

11(15%)

Tal,n=65

GORD

7(11%)

Colic

1(2%)

0Se

izure3(5%)

00

054(83%)

Tsukad

a,n=19*

GORD

6(32%)

Oesop

hage

aldy

sfun

ction2(11%)

Pertussis5(26%)

URTI3

(16%)

Epilepsy1(5%)

0Larnyg

osteno

sis2(11%)

Cho

king

2(11%)

0

V-W

auters,

n=130

GORD

34(26%)

0Se

izure5(4%)

Enceph

alitis1(1%)

Men

ingitis

1(1%)

SAH

1(1%)

0EN

Tinfection2(2%)

Ana

tomical

airw

ayob

struction12(9%)

Brea

thho

lding9(7%)

Vag

alreactio

n2(2%)

Hyp

omag

nesaem

ia1(1%)

Beta

ketothiolase

def.1(1%)

Brea

stmilk

opiates6(5%)

Normal

1(1%)

54(42%)

*Som

einfantsha

dmultip

lediag

noses.

U,un

know

n;includ

esdiag

noseslistedas

‘‘apn

oea’’,‘‘cya

notic

episod

e’’,‘‘p

allor’’,‘‘fun

nyturn’’.

Normal

includ

esdiag

noseslistedas

‘‘Mororeflex’’,‘‘startle

reflex’’,‘‘a

pnoe

amon

itorprob

lem’’.

ASD

,atrial

septal

defect;GE,

gastroen

teritis;GORD

,ga

stro-oesop

hage

alrefluxdisease,

IVH,intraven

tricular

haem

orrhag

e;LRTI,lower

respiratorytractinfection;

PDA,pa

tent

ductus

arteriosus;SA

H,suba

rachno

idha

emorrhag

e;SV

T,supraven

tricular

tachycardia;

UTI,urinarytractinfection;

URTI,up

perrespiratorytractinfection;

VSD

,ventricularseptal

defect.

Firstfig

ureafterdiag

nosisisnu

mbe

rof

times

diag

nosisisrepo

rted

instud

y.Percen

tage

figurein

bracketsisnu

mbe

rof

times

diag

nosisisrepo

rted

instud

y/totaln

umbe

rof

ALTEep

isod

esevalua

tedin

stud

y.Ex

cept

forstud

yB,

numbe

rof

episod

es=nu

mbe

rof

infants.

Apparent life threatening events in infants 1045



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Gastro-oesophageal reflux diseaseThis was reported in every study (n=227, 31% of totaldiagnoses). The diagnosis was assigned after pH studiesonly,8 9 pH studies or barium studies,10 milk scans incombination with clinical findings,5 pH studies or bariumand manometric studies,11 pH studies or manometry.2 In twostudies some infants were assigned the diagnosis on clinicalgrounds.6 7

SeizureThis was reported in seven studies (n=83, 11% of totaldiagnoses), with the eighth describing ‘‘neurological causes’’as a group. Two studies reported abnormal electroencephalo-gram (EEG) findings in the infants with seizures,2 11 but theothers did not describe assignment criteria.

Lower respiratory tract infection (LRTI)The diagnoses ‘‘pertussis’’ and ‘‘respiratory syncytial virusinfection’’ were included under LRTI which was reported infive studies (n=58, 8% of all diagnoses). Pertussis wasdiagnosed by postnasal swab or typical clinical findings witha lymphocytosis,5 bacteriological investigations,2 and byrising pertussis antibody titre.11 One study did not recordassignment criteria.6

Other diagnosesEar, nose, and throat (ENT) problems were reported in sixstudies (n=26, 3.6% of all diagnoses). Cardiac problemswere noted in three studies (n=6, 0.8% of all diagnoses).Urinary tract infections were reported in three studies (n=8,1.1% of all diagnoses) and may have been classified under‘‘infection’’ in a fourth. Metabolic disease was diagnosed infour studies (n=11, 1.5% of all diagnoses), ingestion ofdrugs or toxins was reported in three (n=11, 1.5% of alldiagnoses), breath holding was noted in two (n=17, 2.3% ofall diagnoses), and factitious illness was diagnosed in one(n=2, 0.3% of all diagnoses). Only five ALTE episodes werefelt to be completely benign (0.7% of all diagnoses).

Unknown diagnoses‘‘Diagnosis unknown’’ was reported in seven studies(n=169, 23% of all diagnoses).

Long term follow upDavies and Gupta reviewed the case notes in 98% of infantsafter six months and Gray et al tracked all infants oncomputer for 18 months.5 6 Tal et al followed up all infants for12 months and Veereman-Wauters et al reviewed 22% aftersix months.8 9 Kurz et al and Laisne et al commented onrecurrences and deaths but did not give follow up details.2 7

Recurrences of ALTEs varied between 0 and 24%.2 5 7 8

Five deaths were reported (0.8% of all infants). In onestudy,9 two infants with severe GORD died during sleep, andthree infants in another2 had rare, congenital metabolicdisorders.

DISCUSSIONAn ALTE is a common problem in infancy, often presenting amanagement dilemma, particularly when the infant subse-quently appears well. The history and examination mayprovide clues to the cause, but when they do not, it is difficultto decide how intensively to seek a diagnosis. This systematicreview has identified the common pathological conditionsassociated with an ALTE, highlighted rarer diagnoses to beconsidered, and confirmed that, in a significant number ofinfants, no underlying cause is identified at the initialevaluation.The definition of an ALTE is subjective, and therefore its

incidence is difficult to determine accurately. A prospective

study over two years covering almost 40% of all births inSweden reported an incidence of 0.46/1000 live births, butapnoeic episodes for which medical causes were identifiedwere excluded.12 A retrospective study of severe ALTEs(requiring basic resuscitation) reported an incidence of 0.9/1000 live births.13 From these eight studies, it is clear thatALTEs are a common problem for paediatricians world-wide but, because different measures were used to reportfrequency, no consensus can be drawn about incidence.There was a wide range of diagnoses reported among all

studies. GORD was the most common diagnosis and the onlyone to appear in every study. However, there is littleconsistency in its frequency of diagnosis among studies.This may relate to different investigations for GORD andwhether these were performed in all or selected infants.Other studies have reported incidences of GORD after ALTEsof 42%, 53%, and 54%.14216

Seizure was diagnosed at a more constant frequency thanGORD in most studies, possibly because all clinicians use thesame diagnostic tools. It is well documented that apnoea maybe a manifestation of seizures in infancy, and this review con-firms that investigation for seizures is useful in an ALTE.17220

LRTI was another common diagnosis but again thefrequency of diagnosis varied widely. This may be due toepidemic bronchiolitis or pertussis or because LRTIs wereclassified in one study as ‘‘miscellaneous infection’’.7 Up to20% of infants under six months hospitalised with respiratorysyncytial virus (RSV) infection have been reported to haveapnoea, the association being strongest during the firstmonth of life and in infants born prematurely.21

Inborn errors of metabolism were a small but significantcause of ALTEs in the review. Other authors have diagnosedmetabolic disorders in 7.7% of infants after ALTEs,22 and onestudy based in a metabolic unit found evidence for a possiblefat oxidation disorder in 17% of infants.23

Among the cardiac causes reported, there was just onearrhythmia. There were no reports of a prolonged QTcinterval but only two studies measured this.5 8 It has beensuggested recently that prolongation of the QTc interval inthe first week of life is strongly associated with SIDS, but anyassociation with ALTEs was not explored.24

Although factitious illness or Munchausen by proxy (MBP)was reported in just two children overall, it is vital that childabuse is always considered as part of the differential diagno-sis of an ALTE. This diagnosis is generally made after recur-rent ALTEs, sometimes at tertiary evaluation. MBP has beenreported as a cause of apnoea in 0.27% of infants on homemonitoring programmes,25 and deliberate suffocation anddeliberate poisoning have both been reported as causes ofALTEs.26228

‘‘Unknown diagnoses’’ were reported in seven studies, butthe frequency varied widely (9283%). This may reflectdifferent investigation protocols or assignment criteria. Forexample, a subjective diagnosis like ‘‘breath holding’’ couldbe considered by another clinician as ‘‘unknown diagnosis’’.The term ‘‘apnoea of infancy’’ (AOI) may be used for infantsgreater than 37 weeks gestational age at the onset of apnoeafor which no cause can be identified.1 However, this diagnosisshould not be assigned too readily. Infants with an ALTE forwhich no cause is initially identified may be assigneddiagnoses after specialised investigations.All of the five deaths reported in this review occurred in

infants with an underlying medical problem.However, a comprehensive follow up was reported in three

studies only and so the accuracy of the data on recurrenceand deaths is uncertain. Any relation between sudden infantdeath syndrome and ALTEs is still unclear. Some studies haveshown a slight increase in SIDS after an ALTE, while othershave not.29231




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There were methodological difficulties with the review.Firstly, systematic reviews of diagnoses are often confoundedby a lack of well designed studies, and we anticipated thatthat we would be working with non-randomised studies. Anycase-controlled studies in the literature on the diagnosesafter ALTEs focus on one cause only and their externalvalidity is limited. Secondly, the quality of the eight studiesvaried and, in two,8 9 the primary aim was not to identify thecauses of ALTE. We attempted to apply a validity score usingthe desirable methodological characteristics for studieslooking at disease probability, but were unsuccessful.32

Thirdly, there were difficulties with data extraction. Some

infants had more than one diagnosis and some diagnoses likedevelopmental delay were not specific. Finally, the issue ofcausation must be addressed because the detection of adisorder after an ALTE does not necessarily mean that thetwo are associated. For example, there is conflicting evidenceas to whether or not the relation between GORD and ALTEs iscausal.33 Even when an underlying disorder such as RSVinfection (which seems to have a clear temporal relation withan ALTE) is detected, the question as to why some infantsreact to RSV infection with apnoea while others do not is stillunresolved. It is likely that several factors interact to producean ALTE.

Careful history and examinationRemember to consider child abuse

Check capillary blood glucose

Discharge if:• Examination is normal• Parental anxiety is addressedEnsure follow-up is available

Yes

Is this a first, short, self-correcting episode with feeding?

No

History or examination point tolikely diagnosis

Investigate and manage asclinically indicated

Admit:• Observation and cardiorespiratory monitoring for a minimum of 24 hours• Decide if history or examination point to likely cause

Perform baseline investigations and check child protection register• Blood tests Full blood count and differential count, C-reactive protein, sodium, potassium, urea, calcium, magnesium, glucose, blood gas, ammonia, lactate, pyruvate, blood culture• Urine tests Urinalysis and culture. Toxicology screen. Freeze for metabolic studies if no other diagnosis made• Investigations for LRTI• ECG with measurement of QTc interval• Investigate for gastro-oesophageal reflux• EEG• USS brain

No clues from history or examination

No clear diagnosis and initialepisode severe or recurrent

Consider specialist referral formore invasive investigations

Figure 1 Suggested initial investigation plan for an ALTE in a previously healthy infant.

Apparent life threatening events in infants 1047



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Future directionsHaving determined the diagnoses made at first evaluation ofALTEs, the next step is to address the most appropriate initialinvestigation plan. Other authors have made sugges-tions.5 34239 All emphasise the importance of a thoroughhistory, careful physical examination, and then an initialscreen of investigations in all infants followed by additionalinvestigations in some.Using the diagnoses in table 3, we suggest the investigation

plan shown in fig 1. The use of this approach will depend onthe local availability of the investigations. We estimate that inat least 50% of ALTEs a careful history and examination willpoint to the diagnosis, and emphasise that the thorough (andexpensive) list of investigations in the algorithm are notsuggested for all infants. Also, should one of the initialinvestigations lead to a clear diagnosis, we suggest it is notnecessary to proceed with the others.The subsequent management of an infant with an ALTE

depends on the severity of the initial episode, any diagnosesmade, and whether episodes are recurrent. Specific recom-mendations lie outside the scope of this review, but wesuggest that all parents should be offered training in car-diopulmonary resuscitation and SIDS prevention advice.Home apnoea monitoring may be an appropriate interventionfor some infants.

ConclusionsAn ALTE is similar to other non-specific presenting com-plaints in infancy such as fever. Many pathological condi-tions can trigger an ALTE in infancy. A careful history,examination, and appropriate hospital investigations willenable the clinician to identify many of these disorders, butin a significant number no underlying cause will be identifiedat first presentation. Gastro-oesophageal reflux disease, lowerrespiratory tract infection, and seizures are the most commondiagnoses, but an ALTE may be a presentation of rarerdisorders. Child abuse should always be considered in thedifferential diagnosis. We suggest that it would be useful todevelop and validate an evidence based algorithm of practicalinvestigation of infants presenting with ALTEs.

ACKNOWLEDGEMENTSWe acknowledge the original work of the authors whose studies wereselected for critical review and we thank the experts in the field whokindly supplied us with information when requested. We are gratefulfor help from all of the following: K Blackhall and D Kennedyperformed the literature searches; H Neale retrieved papers; AMcGovern, B Thompson, D Quinn, and A Volprecht translatedforeign language papers; A Talbot and Professor E Trimblecommented on the paper.

Authors’ affiliations. . . . . . . . . . . . . . . . . . . . .

M C McGovern, M B H Smith, Department of Paediatrics, CraigavonArea Hospital, Lurgan Road, Portadown BT63 5QQ, Co. Armagh,Northern Ireland, UK

REFERENCES1 National Institutes of Health. Consensus Development Conference on Infantile

Apnea and Home Monitoring, Sept 29 to Oct 1, 1986. Consensus statement.Pediatrics 1987;79:292–9.

2 Kurz R, Kerbl R, Reiterer F, et al. The role of triggers in apparent life-threatening events (ALTE). Journal of Sudden Infant Death Syndrome andInfant Mortality 1997;2:3–12.

3 Kurz R, Kenner T, Reiterer F, et al. Factors involved in the pathogenesis ofunexpected near miss events of infants (ALTE). Acta Paediatr Hungarica1990;30:435–47.

4 Cohen J. A coefficient of agreement for nominal scales. Educational andPsychological Measurement 1960;20:37–46.

5 Davies F, Gupta R. Apparent life threatening events in infants presenting to anemergency department. Emerg Med J, 2002;19;11216..

6 Gray C, Davies F, Molyneux E. Apparent life threatening events presenting toa paediatric emergency department. Pediatr Emerg Care 1999;15:195–99.

7 Laisne C, Rimet Y, Poujol A, et al. A propos de cent malaises du nourrisson.Ann Pediatr (Paris) 1989;36:451–4.

8 Tal Y, Tirosh E, Even L, Jaffe M. A comparison of the yield of a 24 h versus72 h hospital evaluation in infants with apparent life threatening events.Eur J Paediatr 1999;158(11):954.

9 Veereman-Wauters G, Bochner A, Van Caillie-Bertrand M.Gastroesophageal reflux in infants with a history of near-miss sudden infantdeath. J Pediatr Gastroenterol Nutr 1991;12:319–23.

10 Sheikh S, Stephen T, Frazer A, et al. Apparent life threatening events ininfants. Clinical Pulmonary Medicine 2000;7(2):81–4.

11 Tsukada K, Kosuge N, Hosokawa M, et al. Etiology of 19 infants withapparent life threatening events: relationship between apnea andoesophageal dysfunction. Acta Paediatrica Japonica 1993;35:306–10.

12 Wennergren G, Milerad J, Lagercrantz H, et al. The epidemiology of suddeninfant death syndrome and attacks of lifelessness in Sweden. Acta PaediatrScand 1987;76:898–06.

13 Davis N, Bossung-Sweeney L, Peterson DR. Epidemiological comparisons ofsudden infant death syndrome with infant apnoea. Aust Paediatr J1986;(suppl):29–32.

14 Sacre L, Vandenplas Y. Gastroesophageal reflux associated with respiratoryabnormalities during sleep. J Pediatr Gastroenterol Nutr 1989;9:28–33.

15 Tirosh E, Jaffe M. Apnea of infancy, seizures and gastroesophageal reflux: animportant but infrequent association. J Child Neurol 1996;11:98–100.

16 Haney PJ. Infant apnea: findings on the barium esophagram. Radiology1983;148:425–7.

17 Davis JM, Metrakos K, Aranda JV. Apnoea and seizures. Arch Dis Child1986;61:791–93.

18 Navelet Y, Wood C, Robieux I, et al. Seizures presenting as apnoea. Arch DisChild 1989;64:357–9.

19 Ramelli GP, Donati F, Bianchetti M, et al. Apnoeic seizures as an isolatedmanifestation of epileptic seizures in infants. Eur J Paediatr Neurol1998;2:187–91.

20 Watanabe K, Hara K, Miyazaki S, et al. Apneic seizures in the newborn.Am J Dis Child 1982;136:980–4.

21 Bruhn F, Mokrohisky ST, McIntosh K. Apnoea associated with respiratorysyncytial virus infection in young infants. J Pediatr 1977;90:382–6.

22 Arens R, Gozal D, Williams JC, et al. Recurrent apparent life-threateningevents during infancy: a manifestation of inborn errors of metabolism. J Pediatr1993;123:415–18.

23 Harpey JP, Charpentier C, Paturneau-Jouas M. Sudden infant deathsyndrome and inherited disorders of fatty acid beta oxidation. Biol Neonate1990;58(suppl):70–80.

24 Schwartz PJ, Stramba-Badiale M, Segantini A, et al. Prolongation of the QTinterval and the sudden infant death syndrome. N Engl J Med1998;338:1709–14.

25 Light MJ, Sheridan MS. Munchausen syndrome by proxy and apnea (MBPA).Clin Pediatr 1990;29:162–8.

26 Southall DP, Plunkett MCB, Banks MW, et al. Covert video recordings of life-threatening child abuse: lessons for child protection. Pediatrics1997;100:735–60.

27 Samuels MP, Poets CF, Noyes JP, et al. Diagnosis and management after life-threatening events in infants and young children who receivedcardiopulmonary resuscitation. BMJ 1993;306:489–92.

28 Hickson GB, Altemeier WA, Martin ED, et al. Parental administration ofchemical agents: a cause of apparent life-threatening events. Pediatrics1989;83:772–6.

29 Oren J, Kelly D, Shannon DC. Identification of a high risk group for suddeninfant death syndrome among infants who were resuscitated for sleep apnea.Pediatrics 1986;77:495–9.

30 Dunne K, Matthews T. Near-miss sudden infant death syndrome: clinicalfindings and management. Pediatrics 1987;79:889–93.

31 Southall DP. Home monitoring and its role in the sudden infant deathsyndrome. Pediatrics 1983;72:133–8.

32 Richardson WS, Wilson MC, Guyatt GH, et al. How to use an article aboutdisease probability for differential diagnosis. JAMA 1999;281:1214–19.

33 Amin RS. Gastroesophageal reflux and infant apnea. J Pediatr2000;137:298–300.

34 Wennergren G, Milerad J, Westphall I, et al. Consensus statement on clinicalmanagement. Acta Paediatr 1993;389(suppl):114–16.

35 Brooks JG. Apparent life-threatening events and apnea of infancy. ClinPerinatol 1992;19:809–38.

36 Spitzer AR, Fox WW. Infant apnea; an approach to management. ClinPediatr (Phila) 1984;23:374–80.

37 Guilleminault C, Korobkin R. Sudden infant death: near miss events and sleepresearch. Some recommendations to improve comparability of results amonginvestigators. Sleep 1979;1:423–33.

38 McBride J. Infantile apnea. Pediatr Rev 1984;5:275–84.39 Gibb SM, Waite AJ. The management of apparent life threatening events.

Curr Paediatr 1998;8:152–6.




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ARTICLE

Do All Infants With Apparent Life-ThreateningEvents Need to Be Admitted?Ilene Claudius, MDa, Thomas Keens, MDb

Divisions of aEmergency and Transport Medicine and bPulmonary Medicine, Keck School of Medicine, Childrens Hospital Los Angeles, Los Angeles, California

The authors have indicated they have no financial relationships relevant to this article to disclose.

ABSTRACT

OBJECTIVE. The goal was to identify criteria that would allow low-risk infants pre-senting with an apparent life-threatening event to be discharged safely from theemergency department.

METHODS.We completed data forms prospectively on all previously healthy patients�12 months of age presenting to the emergency department of an urban tertiarycare children’s hospital with an apparent life-threatening event over a 3-yearperiod. These patients were then observed for subsequent events, significantinterventions, or final diagnoses that would have mandated their admission (eg,sepsis).

RESULTS. In our population of 59 infants, all 8 children who met the aforementionedoutcome measures, thus requiring admission, either had experienced multipleapparent life-threatening events before presentation or were in their first month oflife. In our study group, the high-risk criteria of age of �1 month and multipleapparent life-threatening events yielded a negative predictive value of 100% toidentify the need for hospital admission.

CONCLUSIONS.Our study suggests that �30-day-old infants who have experienced asingle apparent life-threatening event may be discharged safely from the hospital,which would decrease admissions by 38%.

www.pediatrics.org/cgi/doi/10.1542/peds.2006-2549

doi:10.1542/peds.2006-2549

KeyWordsapnea, apparent life-threatening event,emergency department

AbbreviationsALTE—apparent life-threatening eventED—emergency departmentSIDS—sudden infant death syndromeHR—hospitalization requiredHNR—hospitalization not requiredOR—odds ratioCI—confidence interval

Accepted for publication Dec 12, 2006

Address correspondence to Ilene Claudius,MD, Division of Emergency and TransportMedicine, Keck School of Medicine, ChildrensHospital Los Angeles, 4650 Sunset Blvd, MS113, Los Angeles, CA 90027. E-mail: [email protected]

PEDIATRICS (ISSN Numbers: Print, 0031-4005;Online, 1098-4275). Copyright © 2007 by theAmerican Academy of Pediatrics

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AN APPARENT LIFE-THREATENING event (ALTE) is de-fined as “an episode that is frightening to the ob-

server and that is characterized by some combination ofapnea (central or occasionally obstructive), color change(usually cyanotic or pallid, but occasionally erythema-tous or plethoric), marked change in muscle tone (usu-ally marked limpness), choking, or gagging.”1 It is un-clear, however, whether an ALTE is a predictor ofsubsequent death, sudden infant death syndrome(SIDS), or some other serious disorder in infants. There-fore, the question of whether infants presenting with anALTE require hospital admission for a thorough diagnos-tic evaluation remains controversial. Hoffman et al2 sug-gested that infant apnea was a risk factor for SIDS.Steinschneider,3 Kelly et al,4 and Burchfield and Rawl-ings5 thought that infants who presented with ALTEswere at high risk for subsequent ALTEs and/or deathresulting from SIDS. Others suggested that ALTEs mayindicate underlying sepsis, pertussis, physical abuse, ar-rhythmias, metabolic diseases, seizures, or even cardiactamponade.6–11 The SIDS rate for infants with ALTEswho required cardiopulmonary resuscitation was foundto be 10% in one study, and it increased to 28% withmultiple ALTEs.11 On the basis of these studies, it becamecommon practice to view infants presenting with anALTE as being at high risk, to admit them to the hospitalfor a diagnostic evaluation, and to consider dischargewith home apnea/bradycardia monitoring.12

In contrast, Hodgman et al13 found that infants withALTEs were not at increased risk for subsequent ALTEs.Southall et al14 studied 2-channel cardiorespiratory re-cordings for infants who died as a result of SIDS, andthey found that SIDS could not be predicted on the basisof the presence of apnea or “abnormal” cardiorespiratoryevents. More recently, the Collaborative Home InfantMonitoring Evaluation Study found that infants withALTEs had no more episodes of apnea than did controlsubjects and that serious cardiorespiratory events did notoccur during the peak incidence of SIDS at 2 to 4 monthsof age.15 These studies cast doubt on the idea that ALTEsare precursors to SIDS or other serious disorders in in-fants. These conflicting results highlight the question ofhow infants with ALTEs should be treated when theypresent to the emergency department (ED).

Many well-written review articles on the topic ofALTEs exist, and consideration of inpatient admission isrecommended strongly by some authors.7,16 However,no prospective study has established that ALTEs recurmore frequently in the days immediately after an ALTEor that these infants require hospital admission. Fewpractitioners would question the need for admission ofan infant who looks unwell or for whom a diagnosisrequiring admission is made in the ED. However, whena child demonstrates normal physical examination re-sults after a suspected ALTE at home, there is a paucityof literature data to support the psychosocial and eco-

nomic burden of a hospital admission. Therefore, weattempted to determine criteria that would allow riskstratification in the ED of patients with ALTEs, into ahigh-risk group of patients who required admission anda low-risk group of patients who could be dischargedsafely if reliable caretakers and follow-up care were en-sured. Although a larger validation set will be requiredto substantiate this in the future, our goal was to createa set of high-risk criteria for patients with ALTEs, with anegative predictive value of �90%, that could deter-mine the need for hospital admission.

METHODSThis study was a prospective observational analysis ofconsecutive patients with ALTEs who presented to theED between July 2002 and April 2005. This study wasapproved by the institutional review board. The NationalInstitutes of Health statement included in the introduc-tion was used to define ALTEs for the purposes of thisstudy.

Our hospital is a tertiary-care, freestanding, academic,pediatric facility with a dedicated ED (annual census:60 000). Of all infants with ALTEs who present to ourED, most are admitted to the hospital, although some arenot. The purpose of this study was to develop criteriathat might predict whether admission was required. Indetermining which patients with ALTEs required admis-sion, 2 primary questions were addressed, as follows.The first involved predictive criteria. What potential pa-tient characteristics could be used to predict the risk ofserious sequelae in infants with ALTEs? These weretested against outcome criteria to determine whetherthey predicted accurately the need for admission. Tostratify risk, we analyzed factors assumed or debated inthe literature to increase the risk of SIDS, including (1)family history of SIDS, (2) patient history of moderateprematurity (gestational age between 30 weeks and 37weeks), (3) previous ALTEs, (4) patient age, (5) presenceof upper respiratory infection symptoms, (6) child’scolor and tone during the ALTE, (7) duration of theALTE, as estimated by observers, (8) interventions re-quired, (9) appearance of the child in the ED, (10)suspicion of child abuse, and (11) multiple ALTEs within24 hours.

The second question involved outcome criteria. Whatoutcomes would be considered to mandate admission?We considered any of the following factors to requireadmission: (1) subsequent events requiring resuscitationduring hospitalization, (2) any subsequent ALTEs and anidentifiable pathologic condition that was treated duringhospitalization, (3) a diagnosis made after admission thatwould have put the patient at risk with discharge andwould normally necessitate admission if identified in theED (eg, child abuse or serious neonatal bacterial infec-tion), or (4) development of a life-threatening condition

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(eg, hypoxemia or respiratory failure) during hospital-ization.

Infants �12 months of age were included if they hada convincing history of an ALTE, as determined by theattending physician in the ED. Infants were excluded fora history of extreme prematurity (estimated gestationalage of �30 weeks was chosen because of the high risk ofpersistence of apnea of prematurity for infants with es-timated gestational ages of 24–28 weeks17), uncorrectedcardiac disease, known seizure disorder, significant de-velopmental delay, or chronic lung disease requiringtreatment. Patients under the care of a neonatologist orpulmonologist because of previous ALTEs were also ex-cluded. All charts were also reviewed by the principleinvestigator to ensure that the child met the definition ofan ALTE and did not meet any exclusion criteria. If achild had an episode of apnea attributable to a clearlydiscernible disease diagnosed by the ED (ie, pertussis),these were not labeled as ALTEs, and the infants werenot included. We included both well- and ill-appearingchildren. Institutional review board-certified personnelwere present 7 days per week, 24 hours per day, tocollect a consecutive sample of patients. No family re-fused consent.

Because this study was purely observational, no mod-ifications were made to the patients’ treatment or dispo-sition because of the study. In the ED, the treating phy-sician completed a form documenting the patientcharacteristics described above. Studies were performedand patients were admitted or discharged at the discre-tion of the attending physician. Discharged patients werecontacted by telephone at 24 to 72 hours, and admittedpatients were observed for additional episodes, results oftesting, and final diagnosis during their hospital stay.Attempts were also made to contact all patients at 1week, to obtain outcome data. Regardless of whetherpatients were actually admitted to the hospital, all pa-tients were categorized as either hospitalization required(HR) or hospitalization not required (HNR), on the basisof the outcome criteria discussed above. Briefly, patientswho required resuscitation during hospitalization, expe-rienced subsequent events attributable to a conditionidentified during hospitalization, or were diagnosed as

having a condition that would have put the patient atrisk of acute deterioration if he or she had been dis-charged were classified as HR. Admitted patients whowere discharged without an imminently life-threateningdiagnosis and experienced either no events or minor,self-resolved events during hospitalization were classi-fied as HNR. Patients discharged from the ED were con-tacted at 24 to 72 hours and, if well and without subse-quent events, were also placed in the HNR category.

Odds ratios (ORs) for the need for hospitalizationwere calculated by using univariate analyses. Multivar-iate analysis was not performed because of the smallnumber of patients who ultimately required hospitaliza-tion in each subset. Significance was tested by usingFisher’s exact tests. In addition, we attempted to developcriteria that would predict with nearly 100% negativepredictive value that a child would not require hospital-ization. The sample size goal was to enroll sufficientpatients to provide a negative predictive value with thelower end of the 95% confidence interval (CI) at 90%.The sensitivity, specificity, and predictive values of thesepooled criteria were calculated with CIs.

RESULTSSixty-four patients were enrolled, and 59 were includedin the final analysis. Of the 5 eliminated, 1 did not meetthe definition of an ALTE, 2 met exclusion criteria, and1 was discharged from the ED and subsequently couldnot be reached; 1 was well without subsequent eventswhen seen 45 hours into the hospital stay, but all sub-sequent records were lost and the treating physiciancould not be contacted. Of the 59 patients in the finalanalysis, 55 were actually admitted to the hospital, and 4were discharged from the ED.

In our analysis, 8 (14%) of the 59 patients wereplaced in the HR category. These 8 patients were alladmitted. Two required PICU transfer, 3 had multiplesignificant apneic episodes while hospitalized, 1 devel-oped an oxygen requirement, and 2 required treatmentfor significant infectious or neurologic conditions. Moreinformation on the patients who required hospital ad-mission is listed in Table 1. The remaining 51 patients didnot experience an event or receive a diagnosis that

TABLE 1 Description of Children Requiring Hospitalization

Patient Age,wk

High-Risk Criteria Reason for Admission/Hospital Course

0.5 Age Multiple apnea/desaturation episodes with GERD, oxygen requirement1 Multiple ALTEs, age Became hypoxemic, oxygen requirement1 Multiple ALTEs, age Seizure, suspected nonaccidental trauma3 Multiple ALTEs, age Intubated because of apnea4 Multiple ALTEs, age Urinary tract infection7.5 Multiple ALTEs Multiple apnea/desaturation episodes with GERD8 Multiple ALTEs PICU for apnea, encephalitis8 Multiple ALTEs Multiple apnea/desaturation episodes with GERD

GERD indicates gastroesophageal reflux disease.

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would have required hospitalization and thus wereplaced in the HNR category. Four of the HNR patientswere discharged from the ED and subsequently con-tacted by telephone, and 47 were admitted.

The most common unifying features of the 8 HRpatients were a history of multiple ALTEs within 24hours of admission (7 of 8 patients) and age of �1month (5 of 8 patients). Prematurity (gestational age of�37 weeks) was also common (3 of 8 patients). Whenthe HR and HNR groups were compared, a history ofmultiple ALTEs and prematurity proved to be signifi-cantly different. An intergroup comparison of the symp-toms studied is listed in Table 2.

Because a history of multiple ALTEs and age of �1month (defined as 30 days) were the most commonfeatures noted among the HR infants, we evaluated theutility of using either of these features as a criterion foradmission. Admitting all patients with ALTEs who were�1 month of age and/or had a history of multiple ALTEswould provide a sensitivity and negative predictive valueof 100% to identify patients who require admission,according to our aforementioned outcome criteria. Be-cause an adverse outcome was a rare event in our pop-ulation, the CI for the sensitivity was large; however, theCI of the negative predictive value was 90% to 100%.Tables 3 and 4 contain the data and the sensitivity,specificity, and predictive values for this tool in identi-fying infants who require admission.

DISCUSSIONOur study shows that only 14% of the patients whopresented to our ED with a diagnosis of ALTE had acondition or subsequent event necessitating hospitaliza-tion. The high-risk criteria (multiple ALTEs within 24hours and age of �1 month) identified each of thosepatients with a negative predictive value of 100%, with

a CI lower limit of 90%. Therefore, the possibility ofbeing able to discharge safely a subset of well-appearing,low-risk patients with ALTEs exists, if the results of thispilot study are borne out in a larger, multicenter popu-lation of patients with ALTEs. In our small group of 59infants, 26 (44%) who did not meet high-risk criteriacould have been discharged safely from the ED.

Several additional patient characteristics were foundto be predictive of subsequent events with calculation ofORs, most notably prematurity (OR: 14) and blue dis-coloration of the face during the ALTE (OR: 4). Thesewere not included in our high-risk criteria, and all pre-mature or cyanotic patients in our study population whorequired hospitalization also met the high-risk criteria.However, prudence suggests that prematurity shouldplay a role in physician decision-making. Similarly, wedid not include ill appearance in our criteria. Five pa-tients looked ill at presentation, and all of those infantsmet the high-risk criteria regardless of appearance.Nonetheless, our personal practice continues to be that achild should be well-appearing and have follow-up careensured to be discharged. No child in this study wasadmitted for social reasons or suspicion of nonaccidentalinjuries; however, these factors may be considerationsfor certain infants with apnea.

Previous studies suggested a higher incidence of SIDSfor patients with a family history11 and higher rates ofsubsequent events for children requiring resuscitation orexperiencing multiple events at home11 and those withprolonged apnea and normal muscle tone during theevent.18 Our study was not powered specifically to assessthis, but we found no association between the degrees ofresuscitation perceived necessary by the parents or themuscle tone during the event and the need for hospital-ization. Although it was not the focus of this study,because it would not affect an ED physician’s decision toadmit a patient in the short term, we attempted to obtainlong-term follow-up data on the patients included. Onethird of the patients were contacted successfully at 3

TABLE 2 Comparability of Patients With ALTEs RequiringHospitalization and Not Requiring Hospitalization

Characteristic No. HR(n � 8)

HNR(n � 51)

P OR for RequiringHospitalization

Mean age, wk 4.1 9.7 .149Age of �1 mo, % 21 62.5 35.3 .127 3.3Multiple ALTEs, % 14 87.5 13.5 .001a 4Prematurity, % 6 37.5 3.9 .009b 14Male, % 35 62.5 56.9 .765 1.3Previous ALTE, % 8 12.5 11.8 .952 1.1URI symptoms, % 23 37.5 35.3 .904 1Turned blue, % 41 87.5 64.7 .198 4.2Tone normal, % 17 37.5 23.6 .405 1.1Duration of �1 min, % 29 25 54.9 .134 0.27Awake previously, % 44 75 72.5 .08 1.13Stimulated, % 39 75 60.8 .445 1.9Given CPR, % 7 12.5 11.8 .952 1.07

URI indicates upper respiratory infection; CPR, cardiopulmonary resuscitation.a Fisher’s exact test, P � .001.b Fisher’s exact test, P � .015.

TABLE 3 Test Characteristics of Age of <1 Month or History ofMultiple ALTEs to Identify Patients Who RequiredHospitalization

Characteristic % (95% CI)

Negative predictive value 100 (90–100)Sensitivity 100 (69–100)Positive predictive value 57Specificity 27

TABLE 4 Data Used for Sensitivity, Specificity, and Predictive Values

No. of Patients

HR HNR

Met high-risk criteria 8 22Did not meet criteria 0 29

682 CLAUDIUS, KEENSby guest on May 3, 2016Downloaded from

months. Of those, 2 HNR patients experienced subse-quent nonfatal ALTEs (one 3 weeks after discharge andone 6 weeks after discharge), and 1 HNR patient devel-oped possible cardiomyopathy 3 months after admission.

Because the vast majority of our patients fared wellthroughout their admissions, the number requiring hos-pitalization was low, which yielded a large CI for thesensitivity of our criteria. However, this does support therarity of subsequent events and life-threatening condi-tions for otherwise asymptomatic ALTE patients and theuse of a negative predictive value to assess the utility ofour work. Ideally, a larger validation set could be testedin a future multicenter study, to confirm our findings.Clearly, the specificity is unacceptably low to be useful;however, our goal was to ensure that all high-risk chil-dren are admitted, and we are willing to accept a lowspecificity to maintain adequate sensitivity and negativepredictive value. The 1 patient who was lost to follow-upmonitoring after being discharged from the ED presentsan additional limitation. Although this child’s outcome isnot known, there is no record of a return visit to our EDor any complaint or legal action initiated within 2 yearsafter the child’s discharge.

CONCLUSIONSOur study showed that only 14% of infants presentingwith an ALTE to the ED had a subsequent clinical coursethat would have required hospitalization for diagnosis orprotection from acute deterioration. All of these caseswere predicted because the infants had multiple ALTEsbefore the ED visit and/or they were �30 days of age.We speculate that most infants who do not meet thesehigh-risk criteria can be discharged safely from the ED.

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9. Cousineau A, Savitsky E. Cardiac tamponade presenting as anapparent life threatening event. Pediatr Emerg Care. 2005;21:104–108

10. Pitetti RD, Maffei F, Chang K, et al. Prevalence of retinalhemorrhages and child abuse in children who present with anapparent life threatening event. Pediatrics. 2002;110:557–562

11. Samuels MP, Poets CF, Noyes JP, et al. Diagnosis and manage-ment after life threatening events in infants and young chil-dren who received cardiopulmonary resuscitation. Br Med J.1993;306:489–492

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13. Hodgman JE, Hoppenbrouwers T, Geidel S, et al. Respiratorybehavior in near-miss sudden infant death syndrome. Pediat-rics. 1982;69:785–792

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15. Ramanathan R, Corwin MJ, Hunt CE, et al. Cardiorespiratoryevents recorded on home monitors: comparison of healthyinfants with those at increased risk for SIDS. JAMA. 2001;285:2199–2207

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PEDIATRICS Volume 119, Number 4, April 2007 683by guest on May 3, 2016Downloaded from

E R R A T A Patel JA, Nair S, Revai K, et al. Association of ProinflammatoryCytokine Gene Polymorphisms With Susceptibility to Otitis Media.PEDIATRICS 2006;118:2273–2279.

Errors occurred in the article by Patel et al, titled “Association of Proinflam-matory Cytokine Gene Polymorphisms With Susceptibility to Otitis Media,”published in the December 2006 issue of Pediatrics (doi:10.1542/peds.2006-0764). In Tables 2 and 3 on pages 2275 and 2276, respectively, the authorsreported the genotypes for TNF-��308 and IL-6�174 incorrectly. For TNF-��308, footnote “c” should be assigned to “G/G” and footnote “d” should beassigned to “G/A or A/A.” For IL-6�174, footnote “c” should be assigned to“G/G” and footnote “d” should be assigned to “G/C or C/C.” On page 2277,Discussion section, second paragraph, line 7, “IL-6�174 GG polymorphism”should be replaced with “TNF-��308 AA/AG polymorphism.”

doi:10.1542/peds.2007-1095

Poehling KA, Szilagyi PG, Grijalva CG, et al. Reduction of FrequentOtitis Media and Pressure-Equalizing Tube Insertions in ChildrenAfter Introduction of Pneumococcal Conjugate Vaccine.PEDIATRICS 2007;119:707–715.

An error occurred in the article by Poehling et al, titled “Reduction ofFrequent Otitis Media and Pressure-Equalizing Tube Insertions in ChildrenAfter Introduction of Pneumococcal Conjugate Vaccine,” published in theApril 2007 issue of Pediatrics (doi:10.1542/peds.2006-2138). On page 715,reference 11 has an error in an author’s name. “Nuorti PJ” should be “NuortiJP.”

doi:10.1542/peds.2007-1030

Claudius I, Keens T. Do All Infants With Apparent Life-Threatening Events Need to Be Admitted? PEDIATRICS 2007;119:679–683.

An error occurred in the article by Claudius and Keens, titled “Do All InfantsWith Apparent Life-Threatening Events Need to Be Admitted?” published inthe April 2007 issue of Pediatrics (doi:10.1542/peds.2006-2549). On page679, in the Results section of the Abstract, on lines 4-6, the authors wrote:“In our study group, the high-risk criteria of age of �1 year and multipleapparent life-threatening events yielded a negative predictive value of 100%to identify the need for hospital admission.” It should read: “In our studygroup, the high-risk criteria of age of �1 month and multiple apparentlife-threatening events yielded a negative predictive value of 100% to iden-tify the need for hospital admission.”

doi:10.1542/peds.2007-1123

1270 ERRATA

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