Newborn IVH/ICH

General information

Aka:

Subependymal hemorrhage (SEH),
Germinal matrix hemorrhage (GMH),
Periventricular-intraventricular hemorrhage (PIVH).

Intraventricular hemorrhage (IVH) arises from extension of SEH through ependymal lining of ventricle and occurs in 80% of cases of SEH.

Aetiology

Germinal matrix (GM)

Germinal matrix - macroscopic and microscopic anatomy

High vascular
Part of the primordial tissue of the developing brain
Source of future neurons and glial cells.
Located just beneath the ependymal lining of the lateral ventricles
Undergoes progressive involution until 36 weeks gestational age (GA).
In premature infants: may persist out of utero

A disproportionate amount of the total CBF perfuses the periventricular circulation through these capillaries which are immature and fragile and have impaired autoregulation.
The site of haemorrhage is age dependent.

Between

24–28 weeks GA: arise over the body of the caudate nucleus
> 29 weeks GA: arise over the head of the caudate nucleus

Prematurity definition by WHO

Extremely preterm (less than 28 weeks)
Very preterm (28 to 32 weeks)
Moderate to late preterm (32 to 37 weeks).

Pathogenesis of PIVH in the pre-term infant

Location

Pre term IVH

Around the GM over the

Head of the caudate (most common)
Thalamus or behind the foramen of Monro

Term-baby IVH

Choroid plexus

Germinal Matrix

The GM starts involution at 34 weeks of gestation.

In case of hypoxic stress, autoregulation fails and excessive perfusion ruptures the GM microcirculation leading to haemorrhage.

In which patients do subependymal germinal matrix (GM) haemorrhages occur?

GM haemorrhage occurs in prematurely born (usually before 34 weeks of gestation)
Low-birth-weight neonates (50% in neonates < 1500 kg) mostly, within the first 3 days after delivery.

Why germinal matrix is a site for bleed:

GM is metabolically active --> susceptible to hypotension and hypoperfusion --> infarction
Receives a major percentage of the cerebral blood flow
Has high levels of tissue plasminogen activator that may impair haemostasis,
Contains fragile microcirculation stroma
GM is a vulnerable watershed zone supplied by

Heubner’s artery: from

Terminal branches of the lateral striate arteries from

Anterior choroidal artery from

ICA/MCA

Why it bleeds in preterm

Postnatal hypoxia

Due to respiratory distress syndrome related to

Hyaline membrane disease,
Pneumothorax and/or
Anaemia

This ischemia to the endothelial cells lining the capillaries makes them vulnerable to infarction and then disruption

Hypercapnia --> maximally dilates the thin-walled vessels of the GM --> sudden increases in perfusion --> rupture of the vessels
Increased venous pressure

From any cause

Labour and delivery,
Positive pressure ventilation,
Stimulation,
Endotracheal suctioning,
Myocardial failure from ischemia

Dehydration followed by rapid resuscitation with hyperosmolar solutions --> sudden increases the intravascular volume (thru' osmotically) --> increases in systemic blood pressure @ GM capillaries --> increased risk of rupture

Deleterious effects of PIVH on the brain are due to

Haemorrhagic damage

Destruction of the germinal matrix and glial precursors
Haemorrhage resorbs may leave patient with porencephaly or cystic lesions

Elevated ICP damage

Diffuse decreased CBF following the haemorrhage due to elevated ICP

Decreased CPP --> periventricular leukomalacia (PVL) and cerebral infarction (periventricular haemorrhagic infarction)

Various HCP damage

Haematoma pressure damage

Reduce CBF to brain pressed by haematoma

Hypoxic damage

Injury from the same hypoxic event that precipitated the PIVH

Seizures: repeated or prolonged seizures may be deleterious to neuronal function

Numbers

Incidence

Depends on the method used for detection (many PIVHs are asymptomatic) and the population being evaluated.
540,000 pre-term infants are born in the United States annually.

85,000 are very pre-term (< 32 weeks GA) and
385,000 are late pre-term (34–36 weeks GA).
Ultrasound (U/S): PIVH in 90% of 113 preemies < 34 weeks gestation

49% were grade III or IV

63,000 very low birth weight (< 1500 grams) infants are born each year.

Of the preemies weighing< 1500 gm birth weight, 20–25% will suffer from a PIVH.
PIVH was found by CT in 43% (20/46) of preemies with birth-weight <1500 gm.

Mortality: 55% vs 23% without PIVH.

Timing

Bimodal distribution.

1st peak: within 6 hours - 12 hours of birth: 50%

Early onset PIVH is more likely to progress and has a higher mortality.

2nd peak: Postnatal 3–4 day
> Postnatal day 4: Only 5% of bleeds will develop
Progression of haemorrhage has been documented in 10–20% of infants.

Grading

Papile et al: most commonly used grading system of Papile et al is based on MRI, CT or U/S findings,

Grade	Description	Risk of progressive hydrocephalus
1	Subependymal	0–10%
2	IVH without ventricular dilatation	15–25%
3	IVH with ventricular dilatation	65–100%
4	IVH with parenchymal haemorrhage	Same grade as 3

Presentation

Asymptomatic (78% 6-month survival)

Most PIVHs are clinically unsuspected (especially with smaller haemorrhages)

Incidental found on surveillance U/S.

May present later with

A fall in Hb
Delays in neurologic development.

Symptomatic (20% 6 month survival)

Acute

Changes in muscle tone or activity: usually decerebrate or decorticate posturing, sometimes flaccid paralysis
Seizures: often subclinical
Tense fontanelle
Hypotension
Respiratory and cardiac irregularities: Apnea & bradycardia (“A’s and B’s”) --> is this a Cushing response?
Unreactive pupils and/or loss of extraocular muscle movements
Hct drop >10%

Subacute

Due to smaller or more slowly developing haemorrhages.
Irritability,
Reduced motor activity
Abnormal eye movements.

Term infants with IVH typically present with

Lethargy or seizures,

Timing of presentation

Most present within 1st week
A small percentage present at birth

Many term infants have no or transient ventricular dilation in the period immediately after IVH but significant proportion may eventually require a shunt, usually during the first year of life.

Hydrocephalus

General information

20–50% of infants with PIVH will develop either transient or progressive hydrocephalus (HCP).

Grades III and IV are more often associated with progressive ventricular dilatation than are lower grades

Low grade PIVH is not HCP free

Younger gestational age infants may be at lower risk.

Mechanism

Post PIVH hydrocephalus usually occurs 1–3 weeks after the haemorrhage.

Communicating HCP

Caused by cellular debris and/or the toxic effects of blood breakdown products on the arachnoid granulations

Non-communicating HCP

Adhesive arachnoiditis in the posterior fossa
Compression or blockage of critical pathways, e.g. at the Sylvian aqueduct

Rare

HCP following intra-uterine PIVH --> aqueduct gliosis --> aqueduct stenosis

Presentations:

Abnormally increasing OFC (crossing percentile curves faster than body weight)

Lethargy

Apnea

Bradycardia

Vomiting

Progressive dilatation of the ventricular system on serial U/S or CT or MRI evaluations.

Differential diagnosis of ventriculomegaly in PIVH

Transient ventriculomegaly:

Occurs in the first few days after PIVH.
This may not cause elevated ICP.
Self limited

Progressive ventriculomegaly:

Occurs in 20–50% of cases
True hydrocephalus

Hydrocephalus ex vacuo:

Due to loss of brain tissue or maldevelopment.
Is not progressive on serial U/S.
OFCs may fall below normal due to lack of growing brain as stimulus for head growth

Diagnosis

Ultrasound (U/S)

Performed through the open fontanelles.

Accuracy ≈ 88% (91% sensitivity, 85% specificity).

Invaluable because:

Demonstrates

Size of the ventricles,
Location and size of the hematoma
Thickness of the cortical mantle

May be brought to the infant’s bedside (obviating transportation)
Non-invasive
It is not adversely affected by occasional infant movements (eliminating the need for sedation)
No ionizing radiation

Radiation from diagnostic imaging in children has long-term risks for cancer and damage to the lens

Can be followed up serially with relative ease

Up to 40 weeks of gestational age the Levene-index should be used and after 40 weeks the ventricular index.

The Levene index is the absolute distance between the falx and the lateral wall of the anterior horn in the coronal plane at the level of the third ventricle.

This is performed for the left and right side.

These measurements can be compared to the reference curve and are quite useful for further follow-up.

After 40 weeks the ventricular index or frontal horn ratio should be used, i.e. the ratio of the distance between the lateral sides of the ventricles and the biparietal diameter.

When using this ratio you have to realise, that when the ventricular system widens, the frontal horns tend to enlarge in the craniocaudal direction more than in the left to right dimension.

Ventricular index

Midline to lateral wall of lateral ventricle

Do not use VI for other diseases

CT scan

Indicated

When U/S is not readily available
Complicated cases where anatomy is difficult to deduce from U/S images.

Many ICUs have portable CT scans available which obviates need for patient transport.

Rapid sequence MRI

Pros:

Eliminates the risk of ionizing radiation associated with CT scan.

Cons:

Requires moving the infant from the neonatal ICU to the radiology suite.

The basics (enough for FRCS!)

Define prematurity

Stratify prematurity

What bleeds?

Where is it?

Why does it bleed?

Grading

Measurement

Risk factors for PIVH

Increased CPP + CBF & hypoxia are the common denominators for most risk factors for PIVH.

The elevated pressure may cause the haemorrhage by rupturing the fragile vessels of the germinal matrix, possibly already damaged by previous insults of high or fluctuating CBF and hypoxia.

Child factors

Increased CBF or CPP by the following:

Asphyxia: including hypercapnia (see above)
Rapid volume expansion
Seizures
Pneumothorax
Cyanotic heart disease (including PDA)
Infants being mechanically ventilated having RDS and fluctuating CBF velocity documented by Doppler flow meter
Anaemia
Decreased blood glucose
Arterial catheterization
Blood pressure fluctuations
Extracorporeal membrane oxygenation (ECMO): due to heparinization in addition to increased CPP
Acidosis

Fragility of blood vessels

Younger gestational age (GA)

Term babies,

15% had peri/intraventricular haemorrhage

Nearly all have grade I/II IVH.

Preterm infants + extremely low birthweight

33% had a history of IVH

Of which 40% was Grade III or IV
But only 3% required VPS

In preterm babies, most IVH occurs within the first 72 h of life and is diagnosed by bedside cranial US due to deterioration over several days.
There is a direct correlation between younger gestational age (GA) and the severity of PIVH.

Gestation age	% of grade 3	% of grade 4
24–26 weeks	32	19
31-32 weeks	11	5

Low birth weight

Acute amnionitis:

Intra-amniotic infection (IAI) is an inflammation of the foetal membranes (amnion and chorion) due to a bacterial infection.

APGAR’s < 4 at 1minute and< 8 at 5minutes

Indicator	0 Points	1 Point	2 Points
Activity (muscle tone)	Absent	Flexed arms and legs	Active
Pulse	Absent	Below 100 bpm	Over 100 bpm
Grimace (reflex irritability)	Floppy	Minimal response to stimulation	Prompt response to stimulation
Appearance (skin color)	Blue; pale	Pink body, Blue extremities	Pink
Respiration	Absent	Slow and irregular	Vigorous cry

Coagulopathies

Iatrogenic

Failure to give antenatal steroids during the 48 hours prior to pre-term delivery (i.e., to women at risk of delivering low birth-weight infants)

General anaesthesia for C-section

Maternal factors

Cocaine abuse

Aspirin use

Prevention

Numerous studies have been conducted to find a method of directly reducing the incidence of PIVH among premature infants. Many are controversial. Optimal resuscitation and neonatal care, with an emphasis on measures which minimize cerebral blood flow fluctuations are key.

Good prenatal care and avoiding pre-term labor

Antenatal corticosteroids:

One course of antenatal corticosteroids to women at risk of having premature birth infants reduces neonatal mortality, respiratory distress syndrome and PIVH.

Multiple courses of antenatal corticosteroids did not improve outcomes and were associated with decreased head circumference, weight, and length at birth

Steroids to stabilize the GM vessels

Indomethacin:

Results in cerebral vasoconstriction + reduces the responsiveness of CBF to changes in CO2 --> lowers CBF and increases arterial oxygenation reducing patent ductus arteriosus (PDA).
However, use is possibly associated with increased risk of intestinal perforation

Antenatal vitamin K given IM> 4 hrs prior to delivery decreases PIVH from 33% to 5%.

Sluicing umbilical cord blood and delaying umbilical cord clamping by 30–120 seconds in premature babies increased hematocrit and decreased PIVH in 5 of 7 studies

Using surfactant to reduce respiratory distress syndrome

Minimizing external stimulation (some centers use fentanyl drips)

Treatment

General measures

Aim:

Optimizing CPP without further excessive elevation of CBF by carefully maintaining normal MAP and normalizing pCO2,
Treatment active hydrocephalus as needed

While daily LPs can control the deleterious effects of post-hemorrhagic HCP, they do not reduce the frequency of long-term HCP (requiring permanent shunting).

Ventricular size must be monitored with serial U/S.

Infants with IVH should be observed closely with

Daily measurement of the occipitofrontal circumference (OFC): increase in growth rate from 0.5 to 1 cm/day for 2-3 consecutive days often suggests symptomatic hydrocephalus.
Bulging fontanelle
Splayed sutures
Episodes of spontaneous apnoea or bradycardia
Refractory seizures
Lethargy
Impaired upward gaze (“sunset” phenomenon)

Recommendation (Mazzola 2014)

Recommendation Concerning Surgical Temporizing Measures: I.

Ventricular access devices (VADs), external ventricular drains (EVDs), ventriculosubgaleal (VSG) shunts, or lumbar punctures (LPs) are treatment options in the management of PHH. Clinical judgment is required.
Strength of Recommendation: Level II, moderate degree of clinical certainty.

Recommendation Concerning Surgical Temporizing Measures: II.

The evidence demonstrates that VSG shunts reduce the need for daily CSF aspiration compared with VADs.
Strength of Recommendation: Level II, moderate degree of clinical certainty.

Recommendation Concerning Routine Use of Serial Lumbar Puncture:

The routine use of serial lumbar puncture is not recommended to reduce the need for shunt placement or to avoid the progression of hydrocephalus in premature infants.
Strength of Recommendation: Level I, high clinical certainty.

Recommendation Concerning Nonsurgical Temporizing Agents: I.

Intraventricular thrombolytic agents including tissue plasminogen activator (tPA), urokinase, or streptokinase are not recommended as methods to reduce the need for shunt placement in premature infants with PHH.
Strength of Recommendation: Level I, high clinical certainty.

Recommendation Concerning Nonsurgical Temporizing Agents. II.

Acetazolamide and furosemide are not recommended as methods to reduce the need for shunt placement in premature infants with PHH.
Strength of Recommendation: Level I, high clinical certainty.

Recommendation Concerning Timing of Shunt Placement:

There is insufficient evidence to recommend a specific weight or CSF parameter to direct the timing of shunt placement in premature infants with PHH. Clinical judgment is required.
Strength of Recommendation: Level III, unclear clinical certainty.

Recommendation Concerning ETV:

There is insufficient evidence to recommend the use of endoscopic third ventriculostomy (ETV) in premature infants with posthemorrhagic hydrocephalus.
Strength of Recommendation: Level III, unclear clinical certainty.

Medical treatment:

Not very effective. Treated patients fared worse in several studies

Effects are short-lived

Osmotic agents: isosorbide, glycerol.

✖ diuretic therapy:

Has been used, but a large study showed increased nephrocalcinosis and biochemical abnormalities, resulting in a borderline increase in the risk for motor impairment at one year.
The results were so compelling, the data-monitoring committee terminated the study prematurely.
Furosemide and acetazolamide therapy was deemed neither safe nor effective in treating post-haemorrhagic ventricular dilatation and cannot therefore be recommended

Surgical

Surgical/interventional treatment for the clot

Evacuation of supratentorial clot

Not done
Poor operative results,
Exception of a posterior fossa haemorrhage causing brainstem compression that does not respond to medical treatment.

Supportive measures are usually in order.

Intervention for intraventricular blood

General information

34% of infants < 1500g require shunt/reservoir drainage after failed medical management.
Grade III and IV PIVH: >70% of cases develop progressive ventricular dilatation, and

32–47% of this subset will ultimately require shunting.

Indications for intraventricular blood

Progressive ventriculomegaly with the OFC crossing percentile curves AND
Clinical evidence of increased ICP (split sutures, tense fontanelle…).

Which temporising device?

ㅤ	Percutaneous tapping?	No abdominal incision?	Internalized hardware?	Continuous drainage?
Ventricular access device	✅	✅	✅	❌
Ventriculo-subgaleal shunt	✅	✅	✅	✅
External ventricular drain	❌	✅	❌	✅
Valveless VP shunt	✅	❌	✅	✅

Serial lumbar punctures

1ST LINE

Used at many facilities for hemorrhages with intraventricular extension and communicating hydrocephalus (the usual type of HCP that occurs with PIVH).

Meta-analysis showed that sequential lumbar or ventricular taps of≈ 10 ml/kg/tap for prophylaxis or treatment of progressive hydrocephalus offers no clear benefit over conservative treatment

Infection rate of 5–9%.

In rare cases, LPs may succeed in temporizing progressive HCP for a few weeks until the infant is large enough for shunt placement.

Infants < 800 gm may not tolerate LPs

Because

Desaturation when lying on their side, OR
LP itself may be difficult.

If so then use 1–2 ventricular taps to at least obtain fluid for analysis

Serial ventricular taps

2nd line

Indicated

Short-term option for those infants who cannot tolerate LPs OR
Obstruction to CSF flow in the lumbar subarachnoid space (e.g. due to spinal subdural hematoma from previous LP).

Not desirable for long-term use because

Repeated trauma to brain --> risk of Porencephaly
Risk of intracerebral, intraventricular, or subdural haemorrhage.

If continued taps are likely

For the following reasons

Large haemorrhage, or
Rapid recurrence of intracranial hypertension as determined by palpation of fullness of anterior fontanelle (AF) following several taps

The acceptable options include:

Continuing serial LPs
Percutaneous ventricular taps: not recommended for more than a few treatments as it causes porencephaly
Temporary ventricular access device (TVAD)

A ventricular catheter connected to a subgaleal reservoir (e.g. a Rickham reservoir, or a low profile McComb reservoir).
These can be inserted safely at the bedside, No need theatre.

Temporary ventricular access:

The reservoir can be used for serial percutaneous taps. Usually tapped QD or QOD.

Use a 27 Ga butterfly needle, clean with at least 3 betadine stick swabs, withdraw ≈ 10ml and send for culture.

Reported infection rate: 8–12%

Advantages of TVAD

Avoids shunt in unhealthy children at risk of

Infection
Skin breakdown
Other operative/anaesthetic complications

Clears protein and cellular debris (more favourable for subsequent shunting)
Avoids repeated penetration of brain with risk of porencephaly
Provides port for infusion of medication (e.g. antibiotics) PRN
Avoids cumbersome, easily dislodged EVD with infection risk 6% on asverage of 13 days of EVD
Up to 25% of patients will recover and avoid permanent shunt placement

Disadvantages of TVAD

Requires services of a neurosurgeon (not always available)
Increases risk of infection of subsequent permanent shunt from 5% to 13%
Inherent risks of surgery including haemorrhage, infection, ventriculitis, meningitis, CSF leak
Risks of over drainage including subdural hematoma, impaired skull growth

Ventricular-subgaleal shunt:

The side-port of the reservoir is left uncapped.
A subgaleal pocket must be created at the time of surgery.
Fluid is reabsorbed from this potential space.
Use has been reported up to 35 days.
Infection rate: ≈ 6%

The reservoir may be converted to VP shunt if and when appropriate.
Not recommended in infants < 1100 gms due to very high infection rate

External ventricular drainage (EVD):

Possibility of inadvertent dislodgment (13%) and
Comparable infection rate (6%)

Early VP shunting not done because:

High infection rate,
Peritoneal cavity not suitable in many cases,

e.g. due to necrotizing enterocolitis (NEC),

Paucity of subcutaneous tissue through which to pass shunt tube… Not recommended for infants < 2000 gms

Technical considerations for serial taps (via ventricular reservoir or LP)

8–20 cc of fluid are removed initially, and this is repeated daily (or more often if AF become very tense before 24 hours elapse) for several days, and then usually varies from 5–20 cc QOD to 15 cc TID depending on response
The frequency and volume of the taps are modified based on:

Fullness of AF:

Attempt to keep AF from becoming tense

Appearance of ventricles on serial U/S:

Strive to prevent progressive enlargement, reduction in size can usually be achieved

Follow OFC:

Should not cross percentile curves

Need to differentiate from the so-called “catch-up phase” of brain growth which may occur once the infant overcomes their overall medical problems and is able to adequately utilize nutrition

Serial U/S will show rapid brain growth without progressive ventriculomegaly in cases of catch-up brain growth

CSF protein concentration:

Controversial.
Diminishes with serial taps.
Some feel that as long as it is ≥ 100mg/dl it is unlikely that significant spontaneous resorption will occur and continued serial taps will probably be needed

Removal of this volume of fluid may cause electrolyte disturbances, primarily hyponatremia --> follow serum electrolytes on a regular basis
Follow with serial U/S on day 3–5, and then weekly for several weeks, and then bi-weekly.

A baseline CT scan is often obtained prior to placement of a permanent shunt.

Insertion of VP shunt or conversion of sub-Q reservoir to VP shunt

Indications:

Symptomatic hydrocephalus or progressive ventriculomegaly
Infant is extubated (and thus off ventilator)
Infant weighs ≥ 2000 grams (some prefer ≥2500 grams)
No evidence of NEC (might create problems with peritoneal end of catheter)
CSF protein ideally < 100mg/dl (because of concerns about plugging of the shunt, or causing ileus or malabsorption of the fluid—which was not seen with high protein fluid shunted from the subdural space188—and also to see if patient will start reabsorbing CSF on their own)

If child is younger than 2 years old

Has increased risk of failure and infection etc
Hence temporize measures as mentioned above before shunting them

Technical recommendations:

Do not tap reservoir for at least 24 hrs before inserting a new ventricular catheter (allows ventricles to expand to facilitate catheterization)
Obtain U/S the day prior to conversion
Use a low or very-low pressure system upgrade later in infancy if necessary
If CSF protein is high, consider a valveless system
Avoid placing shunt hardware in areas on which these debilitated infants tend to lay (to prevent skin breakdown with hardware exposure)

Initially use a low pressure then need to increase the resistance later

Because the intracranial pressure is not high enough to push fluid through the valve

Outcome

Short-term

Preemies with PIVH have higher mortality than matched preemies without PIVH.
The incidence of mortality and progression of haemorrhage is higher the earlier the haemorrhage occurs.
The more severe the haemorrhage, the higher the mortality and the higher the risk of HCP

Short-term outcome of PIVH (≈ 250 cases^147)

Severity of hemorrhage	Deaths (%)	Progressive hydrocephalus (%)
Mild	0	0–10
Moderate	5–15	15–25
Severe	50–65	65–100

Long-term

The effect of low grade PIVH on long-term neurodevelopment has not been studied well.
Most investigators feel that higher grades of PIVH are associated with greater degrees of handicaps than matched controls.

In one study of 12 infants with Grade II PIVH treated with serial LPs and in the 7 with progressive ventriculomegaly with VP shunt followed for a mean of 4.5 years found all were ambulatory and 75% had IQ within normal range.
A recent study of very low birth weight infants showed that children 18–22 months of age with severe PIVH and shunts had significantly lower scores on the Bayley Scales of Infant Development IIR compared with children with no PIVH and children with equal grades of PIVH who did not require a shunt.