1. Neonatology: Hypoxic-Ischemic Encephalopathy, HIE

2. Main Contents Clinical definition Etiology/High risk factors
Pathogenesis and Pathophysiology
Clinical manifestations and diagnostic Neuroimaging
Prognosis
Clinical Management

3. Clinical definition
Brain damage in Fetus and neonates caused by hypoxic and/or decreasing or abruption of blood flow to brain during perinatal period.

4. Etiology Almost all the factors causing asphyxia resulting HIE, and
Maternal
Placenta and umbilicus abnormality
Substantial pulmonary, cardiac and CNS disease of the fetus and neonates
Pronged partum
Medication during delivering

5. High risk factors Prolonged fetal bradycardia
Repeated late decelerations
Low Apgar scores at 5 minutes or later
Low fetal scalp or cord pH
Requirement for prolonged resuscitation with positive-pressure ventilation

6. Pathogenesis and Pathophysiology
Change of cerebral blood flow
normal term stable CBF: 50-60ml/min/100g
CBF＜ 20ml/min /100g, brain damage

7. Pathogenesis and Pathophysiology
Change of cerebral metabolism
Increase in anaerobic glycolysis
Na +, Ca2 + pump function 
intracellular ATP exhausted
Na +, Ca2 + endosmosis
Irritability amino acid
blocking oxidative phosphorylation in mitochondrion
blood stream reperfusion oxygen free radical 

8. Pathogenesis and Pathophysiology
Change of nuropathology
Term baby:
cortex infarction
gray matter in partes profunda necrosis
Preterm:
intraventricular haemorrhage
white matter injury
Cerebral inflammation
IL-1, TNF- , CKs 
Cellular apoptosis 

9. Clinical manifestations
Mild
excitation/ irritability
Apparent at 24 hr
No convulsion
normal EEG

10. Clinical manifestations
Moderate
Convulsion, 50%
with disorder of consciousness
Apparent at hr
Deterioration: intensity of anterior fontanelle
coma

11. Clinical manifestations
Severe
light coma or coma at birth
Irregular respiration and apnea
Convulsion with 12 hr
Poor muscle tone
Intensity of anterior fontanelle
Most die in 1 week
Survivors with severe nerosequelees

12. HIE的诊断—临床表现 1. 胎儿宫内窒息史，严重的胎儿宫内窘迫表现 (胎心＜100次，持续5分钟以上；和/或羊水III度污染)
中华医学会儿科学会新生儿学组 2004年11月修订; 长沙
1. 胎儿宫内窒息史，严重的胎儿宫内窘迫表现
(胎心＜100次，持续5分钟以上；和/或羊水III度污染)
2.  出生时有重度窒息:（Apgar评分1分钟≤ 3分）
至5分钟时仍≤ 5分；或出生时脐动脉血气pH ≤ 7.00 ；
3、出生后24 小时内出现神经系统表现；
4、排除低钙血症、低糖血症、感染、产伤和颅内出血等引
起的抽搐，以及遗传代谢性疾病和其他先天性疾病所引
起的神经系统疾患。
同时具备以上4条者可确诊，第4条暂时不能确定者作为
拟诊病例。

13. HIE的诊断—脑电图 在生后1周内检查 脑电图异常程度与临床分度基本一致 脑电图异常表现： 脑电活动延迟 (落后于实际胎龄)，
中华医学会儿科学会新生儿学组 2004年11月 长沙修订
在生后1周内检查
脑电图异常程度与临床分度基本一致
脑电图异常表现：
脑电活动延迟 (落后于实际胎龄)，
背景活动异常 (以低电压和爆发抑制为主)
振幅整合脑电图 (aEEG)

14. HIE的诊断—影象学检查 头颅B超 可在HIE病程早期 (72小时内) 开始检查 生后4-7天为宜 有利于了解脑水肿、基底神经节丘脑损伤
中华医学会儿科学会新生儿学组 2004年11月修订; 长沙
头颅B超
可在HIE病程早期 (72小时内) 开始检查
有利于了解脑水肿、基底神经节丘脑损伤
和脑动脉梗死等病理改变 CT
生后4-7天为宜
MRI
对HIE病变性质与程度评价方面优于CT

15. Neuroimaging
Cerebral
edema US

16. Neuroimaging
Cerebral
edema CT
MRI

17. Neuroimaging US
injury in Hypothalamus
and Basal ganglia

18. Neuroimaging
injury in Hypothalamus
and Basal ganglia
MRI CT

19. Neuroimaging
injury in Area adjacent to
the sagittal CT
MR I

20. Neuroimaging US
早期回声增强
Cerebral artery
Infarction in terms

21. Neuroimaging
Cerebral artery
Infarction in terms CT
MR I

22. Neuroimaging
PVL in premature US

23. Neuroimaging
PVL in premature CT
MRI

24. Neuroimaging
Punctate encephalon haemorrhage
MRI

25. Severity and diagnosis
中华医学会儿科学会新生儿学组 2004年11月修订; 长沙
Mild　
Irritability, normal tone..
Moro’s:  ; Sucking: normal
normal respiration，no convulsion
Moderate 　
Oppressed，muscle tone ，Moro’s and Sucking 
convulsion。>7-10d, may have sequelae
severe　
coma，frequently convulsion
irregular respiration or apnea.
respiration failure. very high death rate
Survivors usually have sequelae

26. Prognosis Mild and Moderate Recovered <5d, good outcome
Middle >7d,or Severe
worse outcome

27. Clinical Management For an asphyxiated newborn:
immediate maintenance of ventilation and perfusion
control of seizures
maintenance of metabolic homeostasis, especially blood glucose levels to avoid additional cerebral insult

28. Clinical Management Maintenance of adequate ventilation:
Avoidance of hypoxemia and hypercapnia
To avoid systemic hypotension
cerebral perfusion
Prevention of fluid overload:
current data in human newborns do not provide convincing evidence that supports the use of antiedema therapy
Maintenance of normoglycemia

29. Clinical Management Control seizures For refractory seizures:
begin with a loading dose of phenobarbital (20mg/kg) ,IV
followed by additional 5-mg/kg, total dose 40 mg/kg
For refractory seizures:
lorazepam by IV may be indicated
Recent recommendations emphasis:
brief duration of treatment; possible deleterious effects of anticonvulsants on the developing nervous system.

30. Clinical Management Cool Cap (Selective Head Hypothermia Therapy)
Multi-center trial：
US, Canada, UK and New Zealand: 25
Sample: trial/control=116/118
Apgar<=6/5min+Cord arterial ph <7.1
clinical HIE+EEG abnormal
aEEG severe: (n=46)：not effective
aEEG Moderate : (n=172); showed protective
Gluckman PD, Cool Cap trial group. Lancet 2005

31. Clinical Management Cool Cap (Selective Head Hypothermia Therapy)
aEEG Moderate : (n=172); showed protective
Death rate:
severe neromotion disabled 48% vs 66% p=0.02
Bayley MDI: 85 vs 77 p=0.04
Bayley PDI: 90 vs 85 p=0.047
Gluckman PD, Cool Cap trial group. Lancet 2005

32. Clinical Management Whole body Hypothermia NIH Neonatal Network,US
Multi-center：16, sample：208
Results;
Death: 24%(H) vs 36% p=0.08
middle or severe disabled
45%(H) vs 62%(N) p=0.01
(OR: 0.72, 95% CI )
Shankaran et al：National Institute of Child Health and Human Development Neonatal Research Network. 
Whole -body hypothermia for neonates with hypoxic-ischemicencephalopathy. NEJM 2005 Oct 13;353(15):

33. Summery HIE is the major cause of the neonatal death
Asphyxia and ischemia hypoxemia in perinatal resulting in HIE
Diagnosis based on clinical manifestation and may combined with Neuroimaging
Though there are some therapies for HIE treatments for HIE is still not as effective as expected

34. Thanks and questions?