Sudden unexpected death in infancy

1. Sudden Unexpected Death in Infancy
by
Dr. Varughese George

2. Objectives
• Introduction to SUDI, SIDS, Ascertained/ Not
Ascertained Deaths
• Epidemiology
• Classification of SIDU
• Current theories on causation of SIDS
• Forensic Aspects
• Summary

3. Introduction to Sudden Unexpected Death in
Infancy (SUDI)
• Sudden unexpected death of an infant < 1 year of age who
– was healthy.
– not thought to have any life-threatening disease prior to death.
• The definite cause of death is not identified.
• Majority of deaths of young infants occurs between 1 week and 6 months
of age.
• SUDI should be investigated by a multidisciplinary team following a
standard protocol.
• Team should include
– Police/ Social Services.
– Specialist Pediatrician.
– Pathologist/ forensic pathologist.

4. Sudden Death Infant Syndrome (SIDS)
• Sudden unexpected death of an infant < 1 year of age which
remained unexplained even after a thorough case investigation
which includes –
– Complete Autopsy.
– Examination of a death scene.
– Review of clinical history.
• SUDI is often confused for SIDS.
• Infant usually dies while asleep, mostly in the prone or side position
(pseudonyms of crib death or cot death).
• Some pathologists consider infants co-sleeping with a parent as a
exclusion criteria, whereas others don’t.

5. Ascertained/ Not Ascertained Deaths
• Cause of death when death is not explained after full investigation with
consideration of the following factors :
– Child is older/younger than age acceptable for SIDS.
– Atypical clinical features in the history.
– Atypical/Unexplained pathological features.
• Some authors suggest that these could be classified as SUDI.

6. Objectives
• Introduction to SUDI, SIDS, Ascertained/ Not
Ascertained Deaths
• Epidemiology
• Classification of SIDU
• Current theories on causation of SIDS
• Forensic Aspects
• Summary

7. Epidemiology
• The rate of SIDS/ascertained deaths is about
0.5 per 1000 live births.
• Rates of SUDI are also broadly similar across
the world.
• It has been observed 600 infants per year still
die suddenly and unexpectedly in UK of causes
unexplained.

8. Objectives
• Introduction to SUDI, SIDS, Ascertained/ Not
Ascertained Deaths
• Epidemiology
• Classification
• Current theories on causation of SIDS
• Forensic Aspects
• Summary

9. Classification of Natural Infant Deaths
• According to Presentation
Expected
Unexpected
Observed Unobserved
Well Unwell Well Unwell

10. Classification of Natural Infant Deaths
• According to Cause
Commonest causes are
Infections.
Cardiac Diseases.
Respiratory Tract Diseases.
Metabolic Diseases.
Miscellaneous.

11. Infections
• Bacterial infections causing pneumonia, septicaemia and
meningitis is a common cause of death in infancy.
• Bacterial pneumonia preceded by minor respiratory
symptoms causes unobserved death in apparently well
babies.
• The inflammation may not be histologically prominent in early
stages

12. Infections
• Epiglottis due to Hemophilus Influenza is a fairly
common illness
– rare these days due to advent of Hib immunization
programme.
• Babies with meningitis shows some vague and non-
specific symptoms.
• Babies with acute encephalitis may lead to sudden
collapse through invovement of vital structures in the
brain stem.
• Peritonitis may also cause sudden death in infants
with vague symptoms. Pathology includes volvulus ,
Hirschsprung’s disease , meconium ileus,
intussusception,congenital bands etc.
Primary peritonitis typically due to pneumococcus
• Gastroenteritis could cause death as a result of
dehydration which may not be assessed by the family.

13. Infections
• Viral infections are prevalent and fatal, but are less
frequently identified as a cause.
• Viral myocarditis caused by Type B Coxsackie virus
could be fatal.
– Baby may appear non-specifically unwell prior to
collapse in the first few weeks of life.
• Viral encephalitis is usually symptomatic, babies die
before reaching the hospital, having being non-
specifically unwell.
– Enterovirus predominate in first 3 months of life
followed by Herpes simplex after 6 months of life.
– Others - adenoviruses,measles,mumps,rubella
• Viral pneumonitis caused by RSV
is generally symptomatic.
– can lead to apnea in very young/premature infants.

14. Infections
• Babies with asplenia are particular prone to
infections especially pneumococcus.
• A congenital/acquired immune deficit in cases
of overwhelming infection should be
considered as investigation after death,
beyond histopathology could be problematic.

15. Cardiac Diseases
• Undiagnosed congenital heart malformations remain a
common cause of death in 1st week of life.
• Affected babies are poor feeders which may be observed by
their parents.
• Common cardiac disorders which cause sudden collapse are
– Aortic stenosis/atresia
– Hypoplastic left ventricle
– Transposition of the great arteries.
– Anomalous origin of coronary arteries.

16. Cardiac diseases
• Infantile Cardiomyopathy causes SUDI, usually an observed
collapse.
– At autopsy, heart is severely hypertrophic than dilated.
– Possibility of a metabolic /mitochondrial disease should be considered
with appropriate samples taken.
• Endocardial fibro-elastosis typically presents as fetal hydrops,
but occasionally leads to SUDI.
– Possibilty of a metabolic disease should be considered.
– There is an association with maternal autoimmune diorders (Anti-
Ro/Anti-La antibodies)

17. Cardiac diseases
• Cardiac tumors
– may lead to arrhythmias and
severe cardiac enlargement.
– Multiple rhabdomyomas alert the
possibility of tuberous sclerosis
• Disorders of the cardiac
conducting system may lead to
SUDI
– Long QT Syndrome should be
considered if there’s positive
family history of sudden death.
– Family members should be offered
ECG screening and storage of DNA
for genetic analysis.

18. Respiratory Tract Diseases
• Infections of the respiratory tract play a major role in causing SUDI.
• Structural malformations of the upper airways may be associated with respiratory
obstructions
– Choanal Atresia
– Laryngomalacia
– Tracheomalacia
 Noisy breathing/stridor may be apparent
 Condition may be exacerbated by concurrent respiratory infection.
Respiratory failure due to neuromuscular disorders
– Congenital myopathies
– Polymyositis
– Viral myositis
– Anterior horn cell disease.
A careful examination of the respiratory tract is essential.

19. Metabolic Diseases
• Babies are at a risk of sudden cardiac collapse and seizures.
• An unwell infant usually collapses suddenly rather than ‘cot death’.
• Onset is usually in early neonatal period.
• Follows an infectious disease, most often gatroenteritis.
• The baby’ condition deteriorates  drowsy  collapses
• Typically seen in MCAD deficiency, other fatty acid oxidation defect and
mitochondrial disease.
• Fat stains of liver, kidney,muscle & hear should be routine to SUDI workup.
• Ideal biochemical screening of blood and bile by tandem mass
spectrometry should be carried out.

20. Miscellaneous
• Epileptic seizures in infants with known epilepsy may result in sudden
unobserved death.
– Typical features may not be apparent at post-mortem examination.
– Death is more likely in infants with underlying neurological disease than with idiopathic
epilepsy.
– Samples to be taken for anticonvulsant levels.
• Pulmonary vascular disease is difficult to diagnose in early in infancy due
to ongoing vascular remodelling.
– Typically associated with other syndromes
– Smith Lemli Opitz Syndrome.
– Williams Syndrome (Supraclavicular aortic stenosis & abnormal peripheral pulmonary
vessels)

21. Objectives
• Introduction to SUDI, SIDS, Ascertained/ Not
Ascertained Deaths
• Epidemiology
• Classification of SIDU
• Current theories on causation of SIDS
• Forensic Aspects

22. Current Theories on Causation of SIDS
Current favoured theories are : -
• Respiratory Arousal/Brainstem Development.
• Inflammatory mediators/Bacterial toxins.
• Cardiac Arrythmias.

23. Respiratory Arousal/Brainstem Development
Recent studies have shown evidence
of SIDS being a result of
• Failure of normal respiratory
arousal in response to adverse
sleeping environment.
• Failure of normal respiratory
arousal in response to hypoxia in
the first 6 months of life.
• Subtle abnormalities in
development of brainstem could
affect cardiorespiratory centres –
present in at least 50% of SIDS.

24. Inflammatory mediators/Bacterial toxins
Recent studies have shown evidence of SIDS being a result of
• Immune activation
– Increase of inflammatory cells in the lungs.
– Thymic enlargement.
– Raised levels of cytokines
• Abnormal Cytokine response to minor infection
– Excess of high activator alleles of IL-10.
– Polymorphisms in VEGF & IL-6.
• Bacterial infections
– Bacterial toxins trigger SIDS by inappropriate cytokine response as a result
of genetic polymorphisms.

25. Cardiac Arrythmias
Recent studies have shown evidence of SIDS being a result of
• Mutations in genes coding for membrane ion channels.
– LQTS predisposing to cardiac arrythmias  sudden death
– LQTS attributes to 5% of cases classified as SIDS.
– Gene SCN5A could lead to sudden death in sleep.
– Polymorphisms in LQTS genes could result in SIDS.
– Genetic testing of child or ECG screening of close family members is
necessary if there is positive family h/o sudden unexplained/cardiac
death.

26. Objectives
• Introduction to SUDI, SIDS, Ascertained/ Not
Ascertained Deaths
• Epidemiology
• Classification of SIDU
• Current theories on causation of SIDS
• Forensic Aspects
• Summary

27. Forensic Aspects
Suffocation
• Study by carpenter et al identified 87% in their series as
natural
• Pathological appearances of suffocation are commonly
identical to those in a true SIDS – Negative biopsy.
• May be accidental – suffocating with pillow, cushion, hands
• May be inflicted upon as in abuse – a forensic + paediatric
pathologic should take the lead in investigation.
• Rarities include obstruction of airway by a foreign object.
• Careful history & detailed external examination of infants are
essential.

28. Forensic Aspects
Suffocation
External findings
• Facial and conjuctival petechiae - non-specific for upper airway obstruction.
• Facial bruising, pressure marks & abrasions - require an explanation.
• Frank bleeding from upper airways is unusual in the context of SIDS - h/o resuscitation
needs to be excluded.
• Frenulum injury may require careful assessment if intubation has been carried out.
• Natural causes (infection/vascular lesions) should also be excluded.
• H/o co-sleeping with parent should also be considered.

29. Forensic Aspects
Suffocation
Internal Findings
• Severe alveolar hemorrhages
– May be an indicator of airway obstruction
(suffocation) or resuscitation.
– Feature of co-sleeping deaths –
mechanism unclear.
• Haemosiderin- laden
macrophages
- Suggested as a marker of previous upper
airway obstruction though there is no
literature to substantiate this fact.
- Natural causes like pulmonary
hemosiderosis, bleeding disorders &
cardiac disease needs to be excluded.

30. Forensic Aspects
Suffocation
Internal Findings
• The presence or absence of
petechiae – whether thymic ,
cardiac or pleural – has no
diagnostic significance .
• Epidural hemorrhage around
the spinal cord
– May be a postmortem artefact.
– Caused by congestion of epidural
fat network.

31. Forensic Aspects
Co-sleeping Deaths
• This group has increased
incidence with parental co-
sleeping & smoking.
• Legal issues arise if the
carer was under the
influence of alcohol/drugs
• Some infants are vulnerable
to transient airways
obstruction.

32. Forensic Aspects
Munchasen Syndrome by Proxy
• The carer (commonly the mother) causes harm
to the infant to bring it to the attention of the
medical authorities.
• Identification of such cases are extremely
difficult.
• Infants may present with apparent life-
threatening events – poisonings.
• History of apnoeic episodes in infants before
sudden death.
• Attention should be given to any injuries
identified, external airway occlusion being the
commonest pathology.
• Toxicological analysis is essential – should be
done as routine.

33. Summary
• Investigation of SUDI requires a multidisciplinary team.
• Case review by the team can be helpful in refining the diagnosis.
• A full postmortem should be undertaken to an agreed protocol including ancillary tests.
• Tissue should be stored in case DNA is required for genetic tests.
• A diagnosis of long QT Syndrome (LQTS) should be considered if there s a family h/o sudden death.
• Current theories highlight possible role of poor respiratory arousal, inflammatory response/infection/LTQS
for causes of SIDS.
• Suffocation (accidental/deliberate) is difficult to diagnose in this young age group.
• The significance of fresh alveolar hemorrhage & haemosiderin macrophages need to be judged in the light
of all findings & circumstances of death.
• Fresh spinal epidural hemorrhage may be a postmortem artefact.
• Toxicological testing should be routine part of the postmortem examination in SIDS.