Neonatal mortality and encephalopathy
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Transcript of Neonatal mortality and encephalopathy
JEANIE CHEONGNEONATOLOGIST
ROYAL WOMEN’S HOSPITAL, MELBOURNE, AUSTRALIA
Neonatal mortality and encephalopathy
Perinatal mortality related to HIE
Worldwide (Lawn 2010) 5th most common cause of death in children under 5
years 23% per annum since 2000 (≈814,000 deaths in 2008)
New Zealand 2007-2010 14.8% of neonatal deaths attributed to HIE
Neonatal encephalopathy (NE)
Neonatal neurological syndrome Depressed conscious level Abnormal tone and power Feeding difficulties Seizures
Incidence: 1-6 per 1000 live birthsAetiology: Hypoxia-ischaemia (HIE) in 30-50%Outcome:
Death (15%) Severe neurological deficit (25%)
(Badawi 98, Cowan 03, Ferriero 04, Volpe 08)
Clinical evaluationBiochemistryElectrophysiologyNeuroimaging
Diagnostic & Prognostic tools in HIE
Clinical evaluation
Evidence of fetal distress Cord or early neonatal acidaemia Deterioration of fetal heart rate pattern
Sentinel intrapartum event E.g. Uterine rupture, cord prolapse, placental abruption
Depression at birthOvert early neonatal neurological syndrome
Depressed conscious level Abnormal tone and power Feeding difficulties Seizures
Diagnosis: History suggestive of intrapartum insult
(MacLennan 99, Volpe 08)
Duration of fetal acidaemia >1 hourMajor resuscitation
6.4 fold in abnormal neurological outcome Positive pressure ventilation, intubation and CPR in
infants with severe fetal acidaemia
Delayed onset breathing
Prognosis: Resuscitation
(Low 84, Ambalavanan 06, Salhab 04)
Time to onset of breathing
Death or severe neurological deficit
9 minutes 42%20 minutes 88%
Severity of acute encephalopathy syndrome Sensitive for mild or severe encephalopathy Not so for moderate encephalopathy
Seizures 40 fold in adverse sequelae Prognosis worse if early onset and difficult to control ? Greater injury to the brain
seizure burden associated with Lac/Cho & NAA/Cho independent of structural changes on MRI
Duration of neurological abnormalities Low risk if normalisation by 1-2 weeks
Prognosis: Neurologic evaluation
(Finer 83, Levene 86, Robertson 93, Dubowitz 98, Miller 02 & 04, Caravale 03)
“Traditional signs of recovery” Apgar scores Signs of recovery e.g.
Early establishment of suck feedsVisual responsivenessHead growth
have low sensitivity/specificity for predicting neurodisability
Prognosis: Other clinical aspects
(Nelson 81, Mercuri 97, 99 & 00, Stark 06)
Biochemistry
Most biochemical markers have low sensitivity & specificity for diagnosis of HIE
Reflect severity of neurological syndromeE.g.
Glucose, serum lactate, calcium, sodium, pH Excitatory amino acids & creatine kinase-BB in
CSF, inflammatory markers, brain specific proteins (research only)
Diagnosis
(de Praeter 91, Volpe 08)
Increased risk of death or severe disability Hypoglycaemia
If glucose <2.2mmol/L in the first 30 minutes
OR ↑ by 18-fold for death or disability peripheral neutrophil counts in first 96 hrs High % nucleated RBC/WBC High lactate in cord blood
Prognosis
(Salhab 04, Morkos 07, Haiju 08)
Electrophysiology
Patterns reflect pathological varieties of HIE Diffuse cortical & thalamic necrosis
discontinuity, burst suppression, voltage suppression, isoelectric EEG
Periventricular leukomalaciaexcessive sharp waves positive vertex or rolandic
Prognosis Severity & duration of abnormalities Normalisation within 1 week associated with
favourable outcome
Conventional EEG
(Wertheim 94, Biagioni 01, Okumura 02, Caravale 03, Murray 06)
aEEG background pattern: Reflect severity of HI insult Prognostic in the first 6 hours Normalisation within 24 hours in 10-50% of
abnormal aEEG Rapid recovery - good outcome PPV if combined with clinical evaluation or MRI Quantitative aEEG-based index (Cerebral health
index/b)Research tool
Amplitude integrated EEG (aEEG)
(Eken 95, Hellstrom-Westas 95, Toet 99, van Rooij 05, de Vries 05, Shalak 03, Leijser 07, Hathi 09)
aEEG in severe HIE
Seizures Burst suppression
Visual evoked potentials (VEP) & somatosensory evoked potentials (SSEP) Predictive if done within 6 hours
Near infrared spectroscopy (NIRS) Direct measure of cerebral blood flow Predictive if done in the first few days Research tool only
Evoked potentials & NIRS
(de Vries 91, Taylor 92, Eken 95, Meek 99)
Neuroimaging
Abnormalities in HIE Normal (in 50%) Non-specific cerebral oedema “Slit-like” ventricles not prognostic (60% controls) Acute cortical lesions poorly demonstrated
Basal ganglia & thalamic echogenicity
Haemorrhagic necrosis High PPV of poor outcome if persistent
Cranial ultrasound
(Babcock 83, Siegel 84, Eken 94, Rutherford 94)
Pourcelot resistive index (RI) Anterior cerebral artery RI<0.55
Reflects high cerebral blood flow velocityIndicative of severityAssociated with poor outcome
Predictive within 24-48 hours
Cranial ultrasound: Doppler
(Levene 89, Ilves 04)
Doppler: Low RI
Systolic
Diastolic
Patterns of injury in HIE Diffuse cortical neuronal injury: “reversal
sign” Basal ganglia & thalamic injury: ↓
attenuation Not sensitive in mild/moderate HI injury
Computed tomography (CT)
“Reversal” sign “Isoattenuation” of deep nuclear grey matter
Most accurate diagnostic imaging modality
Timing of injury “peripartum” 245 infants with acute NE & intrapartum
HI MRI findings:
80% acute HI lesions4% antenatal lesions4% another disorder16% normal
MR imaging and spectroscopy
(Rutherford 04, Cowan 03)
MRI pattern of injury
Nature of insult Estimated incidence
Outcome
Basal ganglia & thalamus
Severe “prolonged” insult
40-80% Severe cognitive and motor deficits
Watershed white matter & cortex
Prolonged “partial” asphyxia
40-60% Cognitive deficits > motor
Basal ganglia, thalamus, brainstem
Severe abrupt “total” asphyxia
10-20% Mortality 35%Long term feeding problems
Cerebral white matter
Hypoglycaemia, chronic haemodynamic instability
15% Mild cognitive deficits
MRI patterns, nature of insult & outcome
(Rutherford 98, Barkovich 98, Cowan 00, Barnett 02, Martinez-Biarge 11, Volpe 12)
MRI: Severe HIE pattern of injury
Day 4 T2-weighted MRI
MRI: Watershed white matter injury
Day 3 Diffusion weighted MRI (DW-MRI)
Direct measure of brain metabolitesMetabolite profiles not specific to HIEReflect severity of insultPredictive of poor outcome
Lac/Cr, Lac/NAA, Lac/Cho NAA/Cr myo-inositol/Cr
Proton MRS
(Hanrahan 99, Cheong 06, Maneru 01, Miller 02, Robertson 01, Soul 01, Zarifi 02, Barkovich 06)
Conventional T1-W/T2-W imaging Normal on Day 1, abnormal by 3-4 days
Diffusion imaging Abnormalities apparent early “Pseudo-normalise”
Proton MRS Abnormalities appear early lactate (tissue necrosis & cell death) NAA (neuronal & oligodendroglial
injury)
Importance of TIMING in interpretation
32 studies (n=860) Sensitivity (95% CI)
Specificity (95% CI)
Conventional MRI(Day 1-30)
0.91 (0.87-0.94) 0.51 (0.45-0.58)
1H MRS in deep nuclear grey matter (Day 1-30) Lac/NAA **
0.82 (0.74-0.89) 0.95 (0.88-0.99)
Prognostic value of MR biomarkers in HIE
(Thayyil 10)
Late MRI (days 8-30) high sensitivity, low specificity compared with early MRI (days 1-7)
Posterior limb of the internal capsule (PLIC) sign & brain water ADC poor discriminatory powers
Study Day of MRIMedian (IQR)
MRI differences in hypothermia group
Prognostic utility
Rutherford 10(TOBY)
64 cooled67 normothermia
8 (5-11) • basal ganglia, thalamus, white matter, PLIC abnormalities
Predictive accuracy 0.84 (cooled) vs 0.81 (normothermia)
Cheong in press(ICE)
66 cooled61 normothermia
6 (3-7) • white matter & cortical gray matter abnormalities on T1/T2
• No difference in DWI
PPV 88% for T1/T2 & DWI
No effect on prognostic utility with hypothermia
Hypothermia & MRI
MRI/DWI/MRS in HIE
Severe HIE
Moderate HIE
Neonatal encephalopathy (esp HIE) is an important cause of perinatal mortality
Many modalities available in diagnosis & prognosis of HIE
MRI & MRS have greatly improved & refined our ability to prognosticate
However....
Conclusion
“No neurodiagnostic technique is capable of diminishing the
importance of the clinical evaluation of the infant in assessment of
outcome in HIE.
Clinical and specialised diagnostic approaches are of value only when
used in concert”(Volpe 08)