Prematurity, Neonatology, SIDSJay GreenEmergency Medicine Resident, PGY-2July 19, 2007

OutlineApparent Life-Threatening EventsSudden Infant Death SyndromeOther causes of apneaQuick snappers

Wont coverFever/sepsis in the newbornBronchopulmonary dysplasiaCerebral palsyObstructive hydrocehpalus

Case 15mo M, stopped breathing x ?1-2minBlue colour, limpResolved before EMS arrivedNo vomiting, no sz activityPosition - supineNoise - ?chokingNo abnormal eye mvtsNo intervention by parents

Case 1 contOB Hx: no complications, SVD @ 38wksPMH: well childFHxApnea, SIDS, Sz, CHD

Case 1 contO/E:Well-looking childVitalsHR 125, bp 85/55, RR 35, T 369Nothing remarkable to find

Anything specific not to miss O/E?Fundoscopy, SpO2

What is on your differential diagnosis?

Apparent Life-Threatening EventALTE

ALTE DefinitionAn episode that is frightening to the observer and is characterized by some combination of:ApneaColour changeMarked change in muscle toneChokingGagging

National Institutes of Health Consensus Development Conference on Infantile Apnea and Home Monitoring

ALTE Quick StatsIncidence 0.5-6%4-8% of SIDS had a previous ALTENot considered same disease process82% occur between 8am-8pmUsually < 6mo, avg 8-14wksCan be > 1yr13% risk of death if needed CPR and discovered during sleep

ALTE Hx/ExamMost NB parts of ED diagnostic evaluation

HistoryColour, tone, resp effortOnset (sleep, feeding, awake), durationPosition (prone, sitting, supine)Noises (stridor, choking)Eye movementsVomitingIntervention

ALTE - ExamPE usually normal

N = 73Dilated fundoscopic examRetinal hemorrhages in 1pt, child abuse in 4

Back to Case 15mo M ?ALTE

What would you like to do now?Labs?Imaging?Discharge patient?

ALTE Investigations50% have specific diagnosis foundInfection, GI, Sz

ALTE Investigations

196 infants with ALTE, mean age 2mo83% hospital admission50% had normal exam25% had infection/feverDiagnoses:Seizure (25%), GER (18%), febrile convulsion (12%), LRTI (9%), apnea (9%)No infant subsequently died

65 infants with ALTE, mean age 7wks100% hospital admission (required)54% had normal examDiagnoses:GER (25%), unknown (23%), pertussis (9%), Other LRTI (9%), Sz (9%), UTI (8%)No infant subsequently diedThanks Yael!

Investigation protocol13% anemia, 33% WBC (50% had inf)Metabolic screen, urine reducing substances, ammonia not helpfulBicarb in 20% - 7 dx with sepsis/szLactate in 7, 5 had serious illnessU/A, pertussis swab useful in 5% & 8%CXR abN in 9 who had N exam

Return to Case 1Labs NCXR NECG NNasal swab, urine cultures pending

What would you like to do now?

ALTE - Some Perspective

Pre-hospital study, retrospectiveN = 60, mean age 3.1mo83% no distress, 13% mild distress, 3% moderate distressDiagnosesPneumonia (12%), sz (8%), sepsis (7%), ICH (3%), bacterial meningitis (2%), anemia (2%)ALTE can be presenting sign of serious illness, even in well-looking childThanks Yael!

ALTE DispositionMost studies recommend mandatory period of inpatient observationMajority suffer only 1 eventNo single test has a high PPV for detecting anything that will alter the outcomeRecurrence rate for severe ALTE as high as 68% in one studyMore likely in the few days after first event

ALTE Disposition

If no cause for ALTE foundReferred to as apnea of infancyhome apnea-bradycardia monitoringLack efficacy, frequent false alarms, misinterpretation of alarm by parentsPotential candidatesPremature infants exhibiting apnea beyond termTerm infants with ALTE requiring resusSiblings of 2+ SIDS victimsInfants with BPD/tracheostomies

ALTE CausesInfectionSeizureA/W ObstructionBreath-Holding SpellsGERMetabolicNonaccidentalSee EM Reports Aug 7, 2006

ALTE SIDS?Prospective cohort study, N=141, 8yrs?Association between SIDS & ALTEConclusionsRF for all ALTEsCommon to SIDS: single parent, FHx infant death, smoking during preg, marked night sweatingEarly behaviours: repeated apnea, cyanotic episodes, feeding difficulties, marked pallorRF for idiopathic ALTENo common SIDS RFNo subsequent SIDS deaths

ConclusionsALTE/SIDS not part of the same disease processSIDS prevention programs not expected to lower ALTE frequency

ALTE Take-home PointsScary + apnea, colour, choking, toneUsually < 6moWell-looking ALTE ?serious illnessInpatient work-upNot same disease process as SIDS

Questions?

Case 24mo F, found blue, not breathing in cribEMS called, begin CPR, and patch inBaby cyanotic, initial rhythm asystole, no resp effortsWhat do you tell them?Continue CPR and come in?Call it in the field?

Sudden Infant Death SyndromeSudden death of an infant

SIDS Fast FactsUS data0.72/1000 live births in 1998Declining incidence3000 deaths/yr95% < 6-8mo, peak 2-4mo1% < 1mo, 2% > 2yr

What are some risk factors for SIDS?MaternalSmokingDrug useSESAge

SIDS What Happens?>70 theories: triple-risk theory RosensImmature cardiorespiratory controlAutonomic dysfunctionPredisposing factors baroreceptor reflexvasomotor controlcentral venous return, CO, bpSleepExacerbate these effectsProgressive bradycardiaPoor lung perfusion hypoxiaProne sleepURTIOverheatingSIDSPhysiologic stuff

Is sleep ever badI guess so

Various badness that doesnt help

SIDS

Case 2 cont4mo F just arrived in your EDCPR continuingPupils fixed mid-dilatedRhythm asystoleUnknown downtime

How long do you continue the resus?~3 rounds of drugs

SIDS OutcomeAfter infant declared deadBlood, urine, skin samplesFamily meetingCoroner notifiedHouse inspectionAutopsy

SIDS Pathologically SpeakingNothing pathognomonicSome typical findingsPA smooth muscle hypertrophyRVH hepatic hematopoiesis periadrenal brown fatAdrenal medullary hyperplasiaCarotid body abnormalitiesBrainstem gliosis

SIDS EffectsGuilt, blaming, social alienation miscarriage rate, divorce, infertilityPotentially helpful steps:Openly accepting grief reactionsAllowing family to vocalize their feelingsClarifying misconceptionsAllowing the family to hold/be along with infantPrivate place for family to gatherExplanation of cause of death

Case 2 contUnsuccessful resuscitationInfant declared deadParents inform you that infant has a twin brother

What should you do about this?Inform them theres no increased risk?Admit the twin for observation?

SIDS - TwinsCohort studies looking at twinsVariable findings, 2x increased risk of SIDSAny sibling of SIDS victims5-6x increased risk of SIDS

Reasonable to admit the twin for a period of observation

SIDS PreventionNon-prone sleeping (supine preferred)No sleeping in waterbeds, sofas, soft mattresses/surfacesNo soft materials in sleeping envtAvoid bed-sharing and co-sleepingAvoid overheating

Retrospective review, 10yrsAll deaths < 1yr in Quebec396 SIDS deathsInfants 1mo1.4% died sittingP

SIDS Take-home pointsPeak age 2-4moProne sleeping most NB modifiable RFSIDS death can be called in the fieldResus of asystolic neonate x ~3 roundsAdmit twin of SIDS victim

Questions?

Apnea DefinitionsPathological apneaRespiratory pause > 20sec or assoc with cyanosis, pallor, hypotonia, bradycardiaApnea of prematurityPeriodic breathing with pathological apneaApnea of infancyInfant > 37wks, pathological apnea or shorter apneic pauses & bradycardia, cyanosis, pallor, or hypotoniaIdiopathic ALTE

Case 310d F breathing pauses lasting ~5s4-5 episodes/min, comes & goesBorn at 39wksUncomplicated preg/delivery to G1P1No fever, rash, lethargyFeeding well10-12 wet diapers/d, 3-4 seedy stools/dRegained birthweight at 7d

Case 3O/EVS NWell looking child, no apneic episodes in ED

What next?Labs?Imaging?Discharge?What do you think is going on?

Periodic BreathingNormal3 or more pauses of >3sec with less than 20sec of N respirations between pauses

Treatment?Caffeine

MethylxanthinesHelpful in apnea of prematurity and in reducing periodic breathingCaffeine better than theophyllineLonger half-lifeWider therapeutic indexMore reliable absorptionCaffeine citrate 20mg/kg IV/PO load5-8mg/kg ODWhy do we use caffeine?

Caffeine Mechanism of ActionIncreases levels of 35-cyclic AMP by inhibiting phosphodiesteraseCNS stimulant Increases medullary resp center sensitivity to CO2Stimulates central inspiratory driveImproves skeletal muscle contraction Diaphragmatic contractilityPrevention of apnea may occur by competitive inhibition of adenosine

CaffeineN=15 with periodic breathing (PB)ConclusionsWeak correlation btw GER and PBTheophylline/caffeineMarked reduction of PBIncreases GER

Skopnik H et al. Effect of methylxanthines on periodic respiration and acid gastro-esophageal reflux in newborn infants. Monatsschrift Kinderheilkunde 1990;138(3):123-7

Case 44d M apneic episodes today lasting ~30s?A bit blue during episodesDischarged from hospital todayInfant born @ 361 wksUncomplicated preg/deliveryO/EVS N, well child, no apneic episodes in EDInvestigations?Disposition?What does this child have?

Apnea of PrematurityPeriodic breathing with apneic episodes > 20secUsually resolves by 37wks gestationManagement?Inpatient work-up/monitoring Caffeine citrate 20mg/kg IV/PO load5-8mg/kg OD

Apnea Take-home PointsPeriodic breathing is normal3+ pauses >3sec with 20secPathological apnea always deserves W/U

Questions?

Quick Snapper #15d M poor feeding & vomiting x 1dD/C yesterdayBorn 361, difficult labour, decels, forcepsBreast-fed, with bottle supplementationGaining weight x 2dNo bloody stools, non-bilious emesis, no feverO/EVitals NAbdo ?distendedInvestigations?

Quick Snapper #1

Necrotizing Enterocolitis (NEC)Mucosal/transmural intestinal necrosisMost common GI emergency, but often presents prior to d/c90% premature>32wks usually present in 1st week of lifeCan be >3mo in VLBW infants

NEC PathogenesisUnknownProbably combination ofMucosal injury (ischemia, infection, inflammation)Host's response to injury (circulatory, immunologic, inflammatory)RFAggressive enteral feeding, birth-related hypoxic-ischemic insults, infection

NECRadiological appearanceDilated loopsPneumatosis intestinalis (present in 75%)Biliary tract airPneumatosis gastralisFree air (only present in 50-75% with perf)Labs not diagnostic

Treatment?

NEC ManagementConsult peds surgeryAdmissionNPONG/OGCareful fluid/lyte mgmt (3rd spacing)Abx (amp/gent/flagyl)

NEC Take-home Points90% are prematureUsually early but can be >3mo in VLBWPneumatosis intestinalis specific for NECAdmit, NPO, Fluids, NG, Abx, Surgery

Questions?

Quick Snapper #26d F off-colour x 1-2 days - ?jaundiceBorn 386, uncomplicated delivery via C/SFeeding well, 10 wet diapers, 3 stool/dWt regained birth weight todayNo fever, lethargy, irritabilityFHx: nothing metabolic/congenitalO/EWell-looking child, VS NSlight jaundiceInvestigations?

Quick Snapper #2CBC NTotal bili = 200mol/LConjugated bili not elevatedU/A ve

What now?

JaundiceIndications for further work-up?Jaundice appearing

Neonatal JaundiceHUGE differential

What does this infant have?Physiological jaundice60% incidence 1st week of lifeGradual bili increase until 3rd day of lifeBili returns to N ~2wksWhy does this happen?

Quick Snapper #26d FJaundice, otherwise well-lookingBili 200Urine -ve?Physiologic jaundice

Management?

Neonatal Jaundice ManagementContinue breastfeedingMonitoringHomecare, FPPhototherapyExchange transfusions

Complications?Neurotoxicity, encephalopathy, kernicterus

Neonatal Jaundice Take-home Points60% will get physiologic jaundiceConjugated hyperbili is pathologicalJaundice in first 24h of life is pathologicalKnow indications for further W/U

The EndQuestions?

Fundoscopy to detect retinal hemorrhages indicative of traumaThought to be of greater clinical severity/importance if more than just apnea or provided AR/CPRFrightening to observer what isnt??Retrospective review12 month Prospective studyConsider tox screen, CT head, skeletal surveyRecurrence rate for SEVERE ALTE88% only had 1 event in last study (Davies)68% - from EM Reports unable to pull study44 184 controls, looking for shared RF or other common demographic characteristics looked at demographics of ALTEs vs known/suspected SIDS RFALTE and SIDS not part of the same disease process, SIDS prevention programs not expected to lower ALTE frequencyDifficult decision, sometimes gets called in field, some get brought inEthnicity african american, american indian30-50% of SIDS have an infection, usually URTI, 20-30% have gastric contents in the lungsProne sleeping OR 1.7-12.9

Search for metabolic dzGER late post-prandial (>2hrs after meal)Bottom line, true apneic episodes all need work-up and all would be admitted for work-up and observationVLBW < 1500gCBC, lytes, glucose, INR/PTT, BC, UCAbx if ill-appearingW/U smear, Coombs, C/S, lytes, urine for reducing substances, ammonia, TORCHS titers (toxo, rubella, CMV, herpes, syphilis), +/-FSWURapid - >3.4umol/L/hrPhysiologic bili production 2-3x higher in newborns (more rbcs, shorter rbc lifespan), bili clearance is decreased (decreased uridine diphosphogluconurate glucuronosyltransferase (UGT) activity 1% of adult activity at 7d of life, adult level at 14wks of life), increase in enterohepatic circulation of biliBhutani nomogram BF decreases bili by stimulating enterohepatic circulation