1. INTRAVENTRICULAR HEMORRHAGE
What is it?
who is at risk?
Are there complications?
How do we prevent it?

2. Major neurological complication OF PREMATURITY
WHAT IS IT?
Major neurological complication OF PREMATURITY
IVH is a problem that is ALMOST exclusive to prematu
It occurs in 25% to 30% of all very low birth weight preterm infants ,1500 g, and the reported incidence in extremely low birth weight infants ,1000 g is as high as 45%

3. What is it?
Bleed that typically initiates in the periventricular GERMINAL MATRIX
Highly vascularized portion of the FETAL brain which produces brain cells
What does the germinal matrix do?
Between 10 and 20 weeks of pregnancy: it produces neurons that then migrate out to the cortex
Between 23 and 32 weeks: produces glial cells that then act as the foundation for myelin sheaths
In the last 12 to 16 weeks of gestation, the matrix becomes less and less prominent and is essentially exhausted by term. It completely involutes by weeks in most babies.
THIS IS WHY IVH IS IN MOST PART A PROBLEM OF PREMATURITY

4. What is it? Why is the germinal matrix predisposed to bleeding?
+++ blood vessels
Capillary bed characteristically different
Venous drainage
The germinal matrix is not meant for extra-uterine life!
Capillary bed of germinal matrix is composed of large, endothelial lined vessels that are different. These blood vessels are remodelled into real capillaries once the germinal matrix disappears.
Vessels have larger diameter so are more prone to rupture, and are very immature.
Venous drainage of the brain is such that it creates what they call a U-shaped turn in the direction of the blood flow right where that germinal matrix is, so this could be a fragile area and play a role in IVH

5. (BECAUSE THEY HAVE A GERMINAL MATRIX AND AN IMMATURE BRAIN…)
WHO IS AT RISK?
PRETERM BABIES!!
(BECAUSE THEY HAVE A GERMINAL MATRIX AND AN IMMATURE BRAIN…)
So why do some preemies get it and others not??

6. Risk factors PRENATAL POSTNATAL
Maternal infection and chorioamnionitis
Protective prenatal factors:
Pre-eclampsia
Magnesium sulfate??
Antenatal steroids!!
POSTNATAL
Prematurity
RDS
Hypo/hypercarbia
Mechanical ventilation
Inter-hospital transport
Bicarbonate therapy
Pneumothorax
Coag and platelets abnormalities
Resuscitation
BP fluctuations & fluid boluses
Caretaking procedures!!
PDA??
Maternal infection and chorio: increased levels of inflammatory markers and associated with increased risk of IVH
Protective factors:
Pre-eclampsia: enhanced fetal maturation
MgSO4: neuroprotective but nodefinite effect on IVH
Steroids: direct maturational effect on the brain, plus improved resp status
Postnatal:
Prematurity: germinal matrix
RDS: association with IVH due to complications – hypercarbia is potent cerebral vasodilator
BP fluctuations: hypoxia during hypotension, then reperfusion injury (GM vessels rupture). Fluid boluses also cause momentary systemic hypertension. Explain pressure passive state (lack of autoregulaton of cerebral blood flow, high BP = increased CBF)
CARETAKING PROCEDURES CAUSE INCREASED BP!!
MV: asynchronus associated with IVH (causes fluctuations in cerebral blood flow)
Inter-hospital transport: direct association with IVH
Bicarb: hyperosmolar; can cause abrupt elevation in pCO2 (to normalize pH) which would lead to increased CBF
Pneumo: increased intra-thoracic pressure on one side impairs venous drainage from the head
Coag abnorm predispose to bleeding
Resusc:
PDA; no direct association, but can cause HD instability

7. WHO DO WE SCREEN & WHEN?
WHO? ALL BABIES BORN AT: <1500G or < 32 WEEKS (cps)
WHEN? DAY 3, DAY 10, 6 WEEKS (OR TERM)
Why the timing mentioned above?
Highest risk is in the first 3-4 days of life!!! A scan on the 4th day will detect 90% of hemorrhages
All bleeds will have occurred by 10 days of life!!
Maximal extent of the lesion is usually achieved by 3-5 days after initial diagnosis, so a second scan is needed after 4-5 days to determine full extent (this is why 10 days is usually good)
6 weeks: to rule out PVL (complication)

8. By head ultrasound or mri…
DIAGNOSIS
By head ultrasound or mri…
Grading system!

9. GRADING SYSTEMS
PAPILE
VOLPE

10. How does it happen? Progression?

11. What does normal look like?
Sagittal
Coronal

12. What grade?
UNILATERAL GRADE I

13. What grade?
UNILATERAL GRADE II

14. What grade?
BILATERAL GRADE IV

15. What grade?
CT image – bb Kotrotsios
UNILATERAL GRADE III

16. PVL (periventricular leukomalacia) Cerebral Palsy, motor deficits
MAJOR COMPLICATIONS
Hydrocephalus
PVL (periventricular leukomalacia)
Cerebral Palsy, motor deficits

17. HYDROCEPHALUS
… primary characteristic is excessive accumulation of fluid in the brain
the term hydrocephalus is derived from the Greek words "hydro" meaning water and "cephalus" meaning head. As the name implies, it is a condition in which the primary characteristic is excessive accumulation of fluid in the brain. Although hydrocephalus was once known as "water on the brain," the "water" is actually cerebrospinal fluid (CSF) — a clear fluid that surrounds the brain and spinal cord. The excessive accumulation of CSF results in an abnormal widening of spaces in the brain called ventricles. This widening creates potentially harmful pressure on the tissues of the brain.
The ventricular system is made up of four ventricles connected by narrow passages. Normally, CSF flows through the ventricles, exits into cisterns (closed spaces that serve as reservoirs) at the base of the brain, bathes the surfaces of the brain and spinal cord, and then reabsorbs into the bloodstream.
CSF has three important life-sustaining functions: 1) to keep the brain tissue buoyant, acting as a cushion or "shock absorber"; 2) to act as the vehicle for delivering nutrients to the brain and removing waste; and 3) to flow between the cranium and spine and compensate for changes in intracranial blood volume (the amount of blood within the brain).
The balance between production and absorption of CSF is critically important. Because CSF is made continuously, medical conditions that block its normal flow or absorption will result in an over-accumulation of CSF. The resulting pressure of the fluid against brain tissue is what causes hydrocephalus.
 The mechanisms by which hydrocephalus develop include (1) decreased absorption of cerebral spinal fluid (CSF) secondary to obstruction of arachnoid villi by blood and debris or the development of obliterative arachnoiditis (ie, communicating hydrocephalus) and (2) obstruction to CSF circulation (ie, obstructive hydrocephalus).

18. PVL
… characterized by the death of the white matter of the brain due to softening of the brain tissue. It can affect fetuses or newborns; premature babies are at the greatest risk of the disorder. PVL is caused by a lack of oxygen or blood flow to the periventricular area of the brain, which results in the death or loss of brain tissue. 
A major cause is thought to be changes in blood flow to the area around the ventricles of the brain. This area is fragile and prone to injury, especially before 32 weeks of gestation.
Basically creates hole in the white matter
Put babies at risk for motor deficits .. Why?
he periventricular area-the area around the spaces in the brain called ventricles-contains nerve fibers that carry messages from the brain to the body's muscles. Although babies with PVL generally have no outward signs or symptoms of the disorder, they are at risk for motor disorders, delayed mental development, coordination problems, and vision and hearing impairments. 

19. Cerebral palsy & other deficits
The occurrence of cerebral palsy is related to the anatomical structure of the periventricular region of the brain. The cortical spinal motor tracts run in this region. The white matter is arranged such that tracts innervating the lower extremities are nearest to the ventricles, followed by those innervating the trunk, the arm, and, finally, the face. This anatomical arrangement accounts for the greater degree of motor dysfunction of the extremities as compared to the face (spastic hemiplegia in unilateral lesions and spastic diplegia or quadriplegia in bilateral lesions).
Cerebral palsy: Static encephalopathy leading to an evolving motor impairment * Spastic diplegia most common

20. PROGNOSIS & OUTCOMES
Grade I and grade II hemorrhage: Neurodevelopmental prognosis is excellent (ie, perhaps slightly worse than infants of similar gestational ages without PVH-IVH).
Grade III hemorrhage without white matter disease: Mortality is less than 10%. Of these patients, 30-40% have subsequent cognitive or motor disorders.
Grade IV IVH with either periventricular hemorrhagic infarction and/or periventricular leukomalacia (PVL): up to 90% incidence of neurological sequelae including cognitive and motor disturbances
Because of the nature of the injury, prognostication of long-term neurodevelopmental outcomes in preterm infants with PIVH has been an active area of research. Low-grade (mild) PIVH, consisting of grades 1 and 2, were previously believed not to increase the risk of neurodevelopmental impairment (NDI) beyond the risk associated with prematurity alone.13 However, some recent studies have challenged this notion whereas others continue to support the benign nature of mild PIVH. On the other hand, severe grades of PIVH (grade 3 and 4) are well known to be associated with NDI, but there are significant variations in the reported outcomes, which may lead to variability in counseling of long-term outcomes between practitioners

21. HOW CAN WE PREVENT IT? Antenatal steroids Antenatal magnesium sulfate
Pharmacologic
Non-pharmacologic
Antenatal steroids
Antenatal magnesium sulfate
Indomethacin prophylaxis??
Birth of premature babies in tertiary care centers
Restoration of normal oxygenation and ventilation
Avoid bicarbonate infusions
Avoid fluid boluses
Gentle and synchronized ventilation
GOLDEN HOUR/optimal resuscitation
MINIMAL HANDLING
Avoidance of significant rotation of the head in first 72h (maintain neutral head position)
A number of studies have shown that prenatal steroids (2 doses, started 48h before delivery) reduces both the severity and the incidence of IVH. Benefit is attributed to the stabilization of the microvasculature of the germinal matrix and alleviation of disturbance in the cerebral blood flow. It also reduced the incidence of RDS and the need for mechanical ventilation, which in turn reduces risk of IVH
Indomethacin – COX inhibitor (reduced cerebral blood flow – complication- - it attenuates cerebral vascular hyperemic responses induced by hypoxia, hypercapnia, hypertension)
Avoid CO2 less than 40 or pH above 7.4
Head position (minimizes changes in blood flow which could lead to increased or decreased ICP)

22. Questions?