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

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%

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 36-38 weeks in most babies. THIS IS WHY IVH IS IN MOST PART A PROBLEM OF PREMATURITY

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

(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??

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

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)

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

GRADING SYSTEMS PAPILE VOLPE

How does it happen? Progression? http://www.aboutkidshealth.ca/en/resourcecentres/prematurebabies/aboutprematurebabies/brainandbehaviour/pages/intraventricular-hemorrhage-ivh.aspx

What does normal look like? Sagittal Coronal

What grade? UNILATERAL GRADE I

What grade? UNILATERAL GRADE II

What grade? BILATERAL GRADE IV

What grade? CT image – bb Kotrotsios UNILATERAL GRADE III

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

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). http://www.aboutkidshealth.ca/en/resourcecentres/prematurebabies/aboutprematurebabies/brainandbehaviour/pages/intraventricular-hemorrhage-ivh.aspx

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. 

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

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

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)

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