高雄地區第493次小兒科聯合病例討論會

1. Intraventricular Hemorrhage
腦室出血
1
高雄地區兒科聯合病歷討論會
楊書婷主治醫師
高雄醫學大學附設醫院小兒部新生兒科
2023/11/24

2. IVH
has long been recognized as
the major brain abnormalities
responsible for
neurodevelopmental impairments
in VLBW infants
Cystic Periventricular Leukomalacia Worsens Developmental Outcomes of Very-Low-Birth Weight Infants with Intraventricular Hemorrhage-A Nationwide Cohort Study. J Clin Med. 2022. 2

3. IntraVentricular Hemorrhage 腦室出血
IVH remains a common cause of chronic neurologic morbidity.
Despite a gradual decline in the incidence of most grades of
IVH, the increased survival of VLBW infants has resulted in an
increase in the absolute number of infants with IVH.
Avery’s Diseases of the Newborn 10th Ch.60 Brain Injury in the Preterm Infant 3

4. 腦室出血的危險因子
• Very short gestation 週數小
• Male gender 男性
• Vaginal delivery 陰道分娩
• Birth asphyxia 缺氧
• Respiratory distress syndrome 呼吸窘迫症候群
• Pneumothorax 氣胸
• Coagulopathy & thrombocytopenia 凝血功能異常與血小板低下
Avery’s Neonatology 7th Ch.46 Neurological & Neuromuscular Disorders 4

5. 腦室出血的危險因子
• Early hypothermia (may be a marker for prolonged resuscitation)
早期低體溫
• Fluctuating blood pressure and cerebral blood flow with pressure
passive circulation
血壓與大腦血流波動
• Early hypotension and rapid correction 早期低血壓矯正過快
Avery’s Neonatology 7th Ch.46 Neurological & Neuromuscular Disorders 5

6. 腦室出血的Papile 分級法
• Grade I: bleeding is limited to the germinal base
• Echo: a large amount of high echo in the anterior horn
of the lateral ventricle in the coronal plane and caudate
nucleus sulcus in the sagittal plane.
Application of brain ultrasound in premature infants with brain injury. Front Neurol. 2023. PMID: 36860577
• Grade II: intraventricular hemorrhage occurred,
but the ventricle was not dilated.
• Echo: lateral ventricle or choroid plexus patchy or
massive high echo.
6

7. 腦室出血的Papile 分級法
• Severe IVH: grade III-IV
• Grade III: intraventricular hemorrhage with
ventricular dilatation
• Echo: the lateral ventricle was partially or
completely filled with a large amount of hyperechoic
blood and would expand.
Application of brain ultrasound in premature infants with brain injury. Front Neurol. 2023. PMID: 36860577 7
• Grade IV: intraventricular hemorrhage with
periventricular hemorrhagic cerebral infarction
• Echo: a sectorial or spherical hyperechoic zone in the
periventricular white matter.

8. 腦室出血的預後:Low-grade (I-II) IVH
• Microstructural impairment in periventricular & subcortical
white matter
• Size, number & location of these minor lesions might be of great
importance in infants born at the lowest gestational ages
• Matrix injury even after an uncomplicated GMH-IVH results in a
relevant loss of glial precursor cells, leading to impaired
myelination and cortical development
Application of brain ultrasound in premature infants with brain injury. Front Neurol. 2023. PMID: 36860577
8

9. 腦室出血的預後:Low-grade (I-II) IVH
• Much lower risk of developmental disabilities compared to
high-grade IVH
• The outcome of grade I-II IVH needs to be prospectively
studied in relation to the exact description of size and
location in different parts of the matrix protomap of
telencephalic development
Application of brain ultrasound in premature infants with brain injury. Front Neurol. 2023. PMID: 36860577
9

10. 腦室出血的預後:High-grade (III-IV) IVH
• A significantly increased risk of neurodevelopmental
disability, especially when GMH-IVH is complicated by post-
hemorrhagic ventricular dilatation that needs surgical
intervention
• Cerebral palsy rates in infants with grade III IVH: 7-63%
Application of brain ultrasound in premature infants with brain injury. Front Neurol. 2023. PMID: 36860577
Avery’s Diseases of the Newborn 10th Ch.60 Brain Injury in the Preterm Infant 10

11. 腦室出血的預後:High-grade (III-IV) IVH
• Grade III IVH evolve over a period of 1-3 weeks and may
produce a fibrotic reaction that obliterates the
subarachnoid space with subsequent ventricular dilatation
and hydrocephalus
• Grade III-IV IVH are associated with increased mortality
Application of brain ultrasound in premature infants with brain injury. Front Neurol. 2023. PMID: 36860577
Avery’s Diseases of the Newborn 10th Ch.60 Brain Injury in the Preterm Infant 11

12. 腦室出血的預後
• The degree of IVH at birth & the presence of
ventriculomegaly are predictors of neurologic status at a
corrected age of 24 months
• The persistence of ventriculomegaly in grade III-IV IVH is
associated with greater risk of more severe neurologic
sequelae
• 35% of grade III IVH ; 55% with grade IV IVH
• Seizures, cerebral palsy, severe impairment of vision or hearing
Avery’s Diseases of the Newborn 10th Ch.60 Brain Injury in the Preterm Infant 12

13. 腦室出血的處置
• Elimination of factors shown to promote excessive
fluctuations in cerebral blood flow
• Prevention of nosocomial infections
Avery’s Diseases of the Newborn 10th Ch.60 Brain Injury in the Preterm Infant 13

14. 腦室出血的處置:避免大腦血流波動
• Maintenance of blood gases & metabolic status within a normal
range
• Avoidance of excessive suctioning & handling
• Detection & treatment of seizures
• Systemic blood pressure should be maintained with particular
attention to the rate of administration of fluids
Avery’s Diseases of the Newborn 10th Ch.60 Brain Injury in the Preterm Infant 14

15. 腦室出血的追蹤:腦部超音波
• Infants with BBW ≦ 1500 g or GA ≦ 32 weeks
• An ultrasound scan on the 4th postnatal day detects 90% of lesions
• Repeat after 5 days is necessary to establish the extent of the IVH
• Half of infants with ventricular enlargement from IVH develop
rapidly progressive ventricular dilatation during the next 4-8 weeks
Avery’s Diseases of the Newborn 10th Ch.60 Brain Injury in the Preterm Infant 15

16. 臺灣健保現行早產兒腦部超音波審查原則
16

17. 腦室出血的追蹤:腦部核磁共振
• The decision to continue intensive care support is partly
informed by the severity of the IVH & associated brain
injury
• Assessed by cranial ultrasound & MRI examinations
• MRI is the optimal imaging modality to detect smaller
cerebellar hemorrhages & potentially more subtle forms of
noncystic white matter injury
17
Avery’s Diseases of the Newborn 10th Ch.60 Brain Injury in the Preterm Infant

18. 腦室出血的併發症:
Parenchymal Hemorrhagic Infarction (PHI)
• Complicates IVH in 15% of cases.
• All grades can be complicated by PHI
• The higher the grade of IVH, the more likely PHI is to occur
• Caused by venous obstruction induced IVH
• Venous congestion leads to ischemia and to secondary
hemorrhagic infarction.
https://www.researchgate.net/
Cranial ultrasound findings in preterm germinal matrix haemorrhage, sequelae and outcome. Pediatr Res. 2020. 18

19. 腦室出血的併發症:
Parenchymal Hemorrhagic Infarction (PHI)
• High intraventricular pressure due to a large hemorrhage may
additionally affect flow through the subependymal veins, increasing
infarct size.
• Prognosis is highly dependent on location & extent
• Cerebral palsy
• Severe cognitive impairment
• Mortality in infants with extensive PHI is high,
especially when it occurs bilaterally.
Cranial ultrasound findings in preterm germinal matrix haemorrhage, sequelae and outcome. Pediatr Res. 2020.
Magnetic resonance imaging of preterm brain injury. Arch Dis Child Fetal Neonatal Ed. 2003. 19

20. 腦室出血的併發症:出血後水腦
PostHemorrhagic Hydrocephalus (PHH)
• Dilatation of the ventricles subsequent to IVH
• 25% infants with IVH develop progressive PHH (higher with
severe IVH)
• 40% spontaneously resolves
• 15% resolves after non-surgical treatment
• 35% require surgical treatment
• 10% die
Cranial ultrasound findings in preterm germinal matrix haemorrhage, sequelae and outcome. Pediatr Res. 2020
Intraventricular haemorrhage and posthaemorrhagic ventricular dilatation: moving beyond CSF diversion. Childs Nerv Syst. 2021. 20

21. 腦室出血的併發症:出血後水腦
PostHemorrhagic Hydrocephalus (PHH)
• Strongly associated with neurodevelopmental impairment
particularly in infants with
• Persistent PHH that requires surgical intervention
• PHH combined with PHI
Cranial ultrasound findings in preterm germinal matrix haemorrhage, sequelae and outcome. Pediatr Res. 2020.
https://www.researchgate.net/
21

22. 預防腦室出血：產前措施
• Maternal transport 母體轉診
• Avoidance of preterm delivery 避免早產
• Risk of IVH: higher in neonates outborn & transported after birth
• Antepartum transportation to a facility equipped to handle
preterm & VLBW infants may reduce the incidence of
• IVH (13.2% vs 27.4%)
• Severe IVH (32.9% vs 44.1%)
• Compared with infants transferred after birth
22
Pathogenesis and Prevention of Intraventricular hemorrhage Clin Perinatol. 2014 March ; 41(1): 47–67.
Avery’s Diseases of the Newborn 10th Ch.60 Brain Injury in the Preterm Infant
Transport of premature infants is associated with increased risk for intraventricular hemorrhage. Arch Dis Child Fetal Neonatal Ed 2010;95:F403–7.

23. 預防腦室出血：產前措施
• Antenatal corticosteroids 產前類固醇使用
• Associated with a decreased risk of any grade IVH & cerebral
palsy
• The most important intervention to prevent IVH
• 24 hours or more before preterm delivery
• Betamethasone in a total dose of 24mg divided over 24 hours
• The effect is probably due mainly to surfactant production
maturing the fetal lungs
23
Impact of antenatal steroids on intraventricular hemorrhage in very-low-birth-weight infants. J Perinatol 2016;36:352–6.
Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2017;(3):CD004454

24. 預防腦室出血：生產時措施
• Delayed umbilical cord clamping 延遲斷臍
• A reduction in IVH in preterm infants delivered at GA ≧ 35 weeks
• A delay of at least 30-60 seconds
• the American College of Obstetricians and Gynecologists defined in 2017
• Optimize obstetric care & prevent prolonged labor
24
Clamp late and maintain perfusion policy: delayed cord clamping in preterm infants. J Matern Fetal Neonatal Med 2016;29:1705–9
Delayed cord clamping in very preterm infants reduces the incidence of intraventricular hemorrhage and late-onset sepsis: a randomized, controlled trial. Pediatrics 2006;117:1235–42.
Committee Opinion No. 684: delayed umbilical cord clamping after birth. Obstet Gynecol 2017;129:e5–10.

25. 預防腦室出血:適當的神經學照護
• Reduced exposure to hyperventilation, hypocarbia(PCO2<30 mmHg), or
hypoxia 減少過度換氣或缺氧
• Maintenance of adequate mean arterial pressure 維持適當的平均動脈壓
• Prevention of abrupt elevations in cerebral blood flow 避免大腦血流波動
• May be precipitated by excessive handling or tracheal suctioning
• Prevention of risk factors 避免危險因子
• Pneumothorax
• Acidosis
• Rapid infusions of sodium bicarbonate
• Volume expanders
25
Avery’s Diseases of the Newborn 10th Ch.60 Brain Injury in the Preterm Infant

26. 預防腦室出血:避免血壓與大腦血流波動
• Alterations in systemic blood pressure are reflected directly in
changes in cerebral blood flow in preterm because of the impaired
cerebrovascular autoregulation
• A low mean arterial pressure or increased fluctuations of blood
pressure have been associated with an increased risk of IVH.
26
Avery’s Neonatology 8th Ch.50 Neurological & Neuromuscular Disorders; Avery’s Diseases of the Newborn 10th Ch.60 Brain Injury in the Preterm Infant
Use of prenatal phenobarbital in the prevention of subependymal/intraventricular hemorrhage in premature infants. Arch Med Res 1998; 29:pp.247-251

27. 預防腦室出血:避免血壓與大腦血流波動
• Care must be taken to prevent systemic hypertension
associated with excessive handling, suctioning & rapid
infusions of blood or colloid.
• No evidence that pharmacologic manipulation of
systemic blood pressure (e.g., with pressors, steroids,
or volume expanders) to achieve a set goal (e.g., MAP
>30 mmHg) alters the incidence of IVH or improves
neonatal outcome
27
Avery’s Neonatology 8th Ch.50 Neurological & Neuromuscular Disorders; Avery’s Diseases of the Newborn 10th Ch.60 Brain Injury in the Preterm Infant
Use of prenatal phenobarbital in the prevention of subependymal/intraventricular hemorrhage in premature infants. Arch Med Res 1998; 29:pp.247-251

28. 預防腦室出血:適當的呼吸治療
• Reduce exposure to hyperventilation, hypocarbia, or hypoxia
• Mechanical ventilation may be associated with increased risk of IVH
• No significant difference in the rates of more severe grades of IVH
between the HFOV(high-frequency oscillatory ventilation) &
conventional ventilation.
28
Elective high frequency oscillatory ventilation versus conventional ventilation for acute pulmonary dysfunction in preterm infants. Cochrane Database of Systematic Reviews 2015, Issue 3.
Art. No.: CD000104.
★ 依病人呼吸狀況，選擇conventional ventilation或high-
frequency oscillatory ventilation

29. 預防腦室出血:適當的呼吸治療
• Surfactant replacement therapy decrease incidence of IVH &
neonatal mortality in LBW infant
• Since a significant drop in MAP & CBF volume can occur during surfactant
administration, attention should be paid to the speed & volume of
instillation.
★ 針對需使用surfactant但有自主呼吸能力之早產兒，考慮於
NIPPV或NCPAP支持下以minimally invasive surfactant therapy
的方式給予surfactant
29
Avery’s Neonatology 8th Ch.50 Neurological & Neuromuscular Disorders; Avery’s Diseases of the Newborn 10th Ch.60 Brain Injury in the Preterm Infant

30. 預防腦室出血:矯正嚴重的凝血異常或血小板低下
• Abnormal coagulation & platelet function play a role in the
genesis of IVH in some instances
• Therapeutic use of plasma when active bleeding is present or
before invasive procedures
• In those with a risk of significant bleeding & who have an abnormal
coagulation profile
• No current evidence to support prophylactic use of plasma in
association with abnormalities of coagulation tests
30
Avery’s Neonatology 8th Ch.50 Neurological & Neuromuscular Disorders

31. Take Home Massage for IVH
• Most studies have shown IVH, low gestational age & birth
weight to be adversely associated with neurological
development and cognitive impairment in preterm children.
★ The primary goal is prevention of IVH ★
31
Neurodevelopmental outcomes at 6, 12, and 24 months of age in preterm infants with very low birth weights in Taiwan. J Formos Med Assoc. 2022.
Cystic Periventricular Leukomalacia Worsens Developmental Outcomes of Very-Low-Birth Weight Infants with Intraventricular Hemorrhage-A Nationwide Cohort Study. J Clin Med. 2022.
Oct 5;11(19):5886