THAT IS THE JOBTHAT IS THE JOB

SAVING LIVES

MINISTRY OF HEALTH OF UKRAINELUGANSK STATE MEDICAL

UNIVERSITYDEPARTMENT OF PEDIATRICSREPORT PRESENTED BY RUBEN

GOMBALANDI .SUPERVISED BY Dr. OKSANA

BABINOVA. ON

OBJECTIVE• INTRODUCTION• DEFINITION• EPIDEMIOLOGY • DEMOGRAPHIC• PATHOPHYSIOLOGY• AUTONOMIC CONTROL AND AROUSAL• AUTOPSY FINDING• NEUROANATOMICAL FINDINGS• RISKS FACTORS• GENE ENVIROMENT INTERACTION• DIAGNOSIS• PREVENTION• MANAGEMENT AND SUPPORT • FUTURE DIRECTIONS• REFERENCE

INTRODUCTION

Sudden infant death syndrome continues to be the most common cause of post neonatal death, account for 25% of all death between 1month of age and 1 year of Age.SIDS is a complex, multifactorial disorder of which the cause is not fully understood.Some environmental risk factors are modifiable

Reducing exposure to modifiable risk factors has lowered the incidence of SIDS

New research indicates genetic risk factors Actual risk of SIDS may depend on interaction of environmental and genetic risk factors

DEFINITIONSudden death of an infant under 1 year old that is unexpected by history and unexplained after a thorough post mortem examination

INVESTIGATION

Investigation includes:Complete autopsyInvestigation of the scene of deathReview of medical history

EPIDEMIOLOGYSIDS rate in United States

1990 – 1.3 per 1000 live births2002 – 0.6 per 1000 live births~ 3000 SIDS deaths/yr

Changes in classification of sudden unexpected deaths in infants from SIDS to categories of asphyxia and “unknown” has occurred in recent years

May be falsely reducing SIDS rates while overall death rate from unexpected infant deaths remains the same

DEMOGRAPHY

less frequently in 1st month of lifePeaks 2-4 month of age90% in first 6 months of lifeBoys 30-50% more likely to be affected than girls Racial and ethnic disparities

2-3x risk for African American, Native American or Alaska Native (irrespective of socioeconomic status)African Americans twice as likely to place infants prone to for sleep & twice as likely to bedshareHigh rates of smoke exposure and bedsharing among Native Americans and Alaskan NativesAsian, South Pacific, Hispanic infants lowest incidence

Winter seasonal predominance has declined or disappeared

PATHOPHYSIOLOGY

Multifactorial in origin

Triple Risk HypothesisVulnerable infantCritical developmental period in homeostatic controlExogenous stressors

Final pathway believed to involve immature cardiorespiratory and autonomic control along with failure of arousal responsiveness from sleep

AUTONOMIC CONTROL AROUSALSIDS infants higher baseline heart rates, lower heart rate variability, prolonged QT indexes, lower parasympathetic tone and/or high sympathovagal balanceAbnormalities of arousal

Kato and colleagues report infants who died of SIDS had fewer spontaneous arousals from sleep and immature sleep patterns

Prone sleeping Increases total time infants spend asleep particularly time spent in quiet sleep, a state of reduced arousability Also decreased spontaneous arousability, induced arousability and fewer full cortical arousals Associated with altered autonomic control manifest by raised heart rates, decreased heart rate variability and increased sympathetic tone

Infants exposed to smoking in utero have decreased spontaneous and stimulus-induced arousal from sleep

A GOOD NUMBER SIDS VICTIM

Child AUTONOMIC NERVOUS SYS

AUTOPSY FINDINGSNo pathognomonic findingsCommon findings:

Petechial hemorrhages of thymus gland, visceral pleura in 68-95%Pulmonary congestion (89%) and edema (63%) indicative of terminal left ventricular failureOronasal secretions that are typically frothy, mucoid and pink or bloody2/3 structural evidence of pre-existing, chronic low-grade asphyxia

Study identified increased VEGF in CSF of SIDS infants, 308 versus 85 pg/dL in controlsHypoxia frequently precedes death in SIDS

One study of 20 SIDS infants found 50% had levels of IL-6 in CSF equivalent to those found in infants who died of infectious diseases

Staphylococcus aureus may have role in infection as 56% of healthy infants and 86% of SIDS infants had these bacteria in the respiratory tract

NEUROANATOMICAL FINDINGS

Structural and neurotransmitter alterations in brainstem consistent with autonomic dysregulation

Increase in dendritic spines (marker of delayed neuronal maturation) and delayed maturation of synapes in medullary respiratory centersDecreased tyrosine hydroxylase immunoreactivity in catecholaminergic neuronsIncreased number and density of 5-HT neurons with decreased serotonin 1A and 2A receptor

Serotonin affects various autonomic functions including cardiorespiratory and circadian rhythms

MORE FINDINGS60% SIDS cases hypoplasia of arcuate nucleus

Vital area of autonomic control and integrationReceptor abnormalities relevant to autonomic control

Decreases in binding to kainate, muscarinic cholinergic and 5-HT receptors

Lavezzi showed alterations of the cerebellum62% of SIDS compared to 10% controls showed neuronal immaturity, altered apoptotic programs, negative expression somatostatin and EN2 gene, intense c-fos expression and astrogliosis in cortex and dentate nucleus

Water reported increased neuronal apoptosis in hippocampus and brainstem

Neuronal loss in regions sensitive to hypoxia and regions associated with sensation in the face

RISKS FACTORS

RISKS FACTORS DIVIDED INTO:

SOCIAL FACTORSIncreased risk with:

Lower socioeconomic statusYounger maternal ageLower maternal educationSingle marital status

MOTHER RELATED FACTORSMothers of SIDS infants:

Less prenatal careCare initiated later in pregnancyLow birth weightPreterm birthIUGRShorter intervals between pregnancies (< 18 mo) More often 2nd or higher order birth child

SUBSTANCE USE AS A PREDISPOSING FACTOR

INFANT SLEEP PRACTICE AND ENVIROMENT

Prone sleeping consistently shown to increase risk of SIDSHighest risk when usually placed in another sleeping position but were placed on stomach for last sleep, “unaccustomed prone”, more likely to occur outside the home such as day care centersAlso risk of choking highest in prone position

Placing infant on side still places risk twice as likely to die of SIDS compared to sleeping supine

Exceptions may be made with certain medical conditionsSoft sleeping surfaces 2 to 3 fold increase risk of SIDS

Prone sleeping + soft bedding 20 fold increaseOverheating with increased room temperature, high body temperature, sweating or excessive clothing increase incidence

No increase with high external environment temperatureNo protective effect from bed sharing

Advocates of this practice typically promoters of breast feeding1/3 reduction with sleeping in parent’s bedroom in separate crib

INFANT FEEDING PRACTICE AND EXPOSURE

Association between breast-feeding and SIDS inconclusiveRecent study showed breast-feeding associated with decreased risk of postneonatal deaths overall but not decreased risk of SIDS

Decreased risk with pacifier useNot known whether direct effect or associated infant or parental behaviorsPacifier use and dislodgement may enhance arousabilityNo association between pacifier use and breast-feeding durationSmall increased in otitis media, respiratory tract and GI tract illnessesMust use consistently, one study showed increased risk of SIDS if pacifier was not used before last sleepAAP recommends pacifier use once breast-feeding has been established

GENE ENVIROMENT INTERACTION

GENETICS RISK FACTORS

Sodium (SCN5A) and Potassium channel polymorphisms associated with long QT syndrome

5-10% of SIDS cases associated with defective cardiac ion channel with increased potential for lethal arrhythmia

Polymorphisms in serotonin transporter (5-HTT) geneIncreased in transporter activity, reducing 5-HT concentrations at nerve endings

Autonomic nervous system development genes (PHOX2A, RET, ECE1, TLX3, EN1)Polymorphisms in promoter of anti-inflammatory cytokine IL-10 decreased antibody production and increased inflammatory cytokinesSIDS infants w/mild respiratory infections before death were more likely than SIDS infants without infection and controls to have deficient complement C4 gene (C4A, C4B)

DIAGNOSIS

By definition, SIDS is a diagnosis of exclusionProtocols for standardized autopsies and death scene investigations have been publishedHowever, wide variability in protocols in both content and frequency with which they are implemented across jurisdictions, within countries and across different countries Cause of death can be difficult to diagnose from autopsy alone

Examination of circumstances present immediately before death including detailed description of sleep environment have been increasingly emphasized in recent years

Surveys of medical examiners and coroners have reflected how much more complicated, confusing and time consuming SIDS case have become

Most also noted they used to label many more infant death cases as SIDS than they do nowThis may be an effect of confusing risk factors for SIDS

Reaching consensus internationally on a classification scheme is essential to accurately monitor trends and direct future research

RISK REDUCTIONCampaign to reduce risk of SIDS began in 1994 in the United States

Largely focused on reducing prone sleeping and promoting supine positioningSome campaigns also included messages to reduce smoking during pregnancy

No significant changes in these behaviors and reduced SIDS rates mostly attributed to avoidance of prone sleeping

Breast-feeding advocates have opposed discouraging bed sharing as they worry these measures will reduce breast-feeding frequency and duration and prevent families from enjoying the experience and benefits of bed sharing

FUTURE DIRECTIONS

Despite decrease in prevalence of SIDS, more work is neededElucidation of risk and protective factors with appropriately targeted and implemented interventions leading to increased adoption by familiesUnlikely disorder is completely eliminated or reduced to lowest possible rates until specific causative mechanisms are more fully understood

Need studies with larger sample sizes and infants from highest risk groupsInvestigations of still births and sudden unexplained deaths in children over 1 year of age might provide additional insights

Surveillance of trends in rates of SIDS comparisons across jurisdictions and internationally according to a universal, standardized classification protocol Will require multidisciplinary and collaborative effort to understand more

REFERENCE Hunt CE, Hauck FR. Sudden infant death syndrome. Cmaj. Jun 20 2006;174(13):1861-1869.Moon RY, Horne RS, Hauck FR. Sudden infant death syndrome. Lancet. Nov 3 2007;370(9598):1578-1587.Weese-Mayer DE, Ackerman MJ, Marazita ML, Berry-Kravis EM. Sudden Infant Death Syndrome: review of implicated genetic factors. Am J Med Genet A. Apr 15 2007;143A(8):771-788.Gurbutt D, Gurbutt R. Risk reduction and sudden infant death syndrome. Community Pract. Jan 2007;80(1):24-27.Fleming P, Blair PS. Sudden Infant Death Syndrome and parental smoking. Early Hum Dev. Nov 2007;83(11):721-725.Damato EG. Safe sleep: can pacifiers reduce SIDS risk? Nurs Womens Health. Feb 2007;11(1):72-76.