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Grades I and II are defined as mild IVH, and grades III and IV as severe. Patients with
severe IVH have poorer neurodevelopmental outcome than patients with milder IVH.
(See 'Outcome' below.)
PREVENTION OF IVH
Prenatal and delivery room interventions The most effective strategy to prevent IVH
is prevention of preterm birth. When preterm birth cannot be avoided, the following prenatal
and delivery room interventions are associated with a reduced risk of IVH.
In one study of 106 preterm infants delivered by cesarean section, the absence or
presence of active labor did not affect the overall incidence of IVH. However, active
labor was associated with a higher risk of severe IVH [ 10 ].
In contrast, a study of ELBW infants demonstrated labor did not affect the risk of
severe IVH when controlling for confounding maternal and neonatal factors (eg,
birth weight, the administration of antenatal steroids, gestational age, and birth at
an outside hospital) [ 11 ].
General neonatal care Although evidence based on clinical trials is limited, it is widely
accepted that the following general measures reduce the risk of IVH after birth based on the
understanding of the pathogenesis (eg, hemodynamic instability) and risk factors (eg,
acidosis) associated with IVH [ 1 ]. (See "Clinical manifestations and diagnosis of
intraventricular hemorrhage in the newborn", section on 'Pathogenesis' and "Clinical
manifestations and diagnosis of intraventricular hemorrhage in the newborn", section on
'Risk factors' .)
Metabolic abnormalities, especially those that cause fluid shifts across cell
membranes (eg, hyperosmolality, hyperglycemia, and hypoglycemia), should be
prevented. Acidosis or alkalosis should be corrected carefully. Bicarbonate therapy
should also be avoided in preterm infants because it is associated with an
increased risk of IVH. (See "Acute kidney injury (acute renal failure) in the
newborn", section on 'Metabolic acidosis' .)
Fresh frozen plasma (FFP) given in response to abnormal coagulopathy tests at two
hours of life resulted in decreased occurrence of IVH (34.5 versus 61 percent) in a
group of 23 to 26 week premature infants [ 14 ].
Recombinant activated Factor VII has been tested as a potential treatment for
newborns with IVH, but large randomized trials have not been conducted yet to
demonstrate efficacy or safety.
Although postnatal indomethacin appears to decrease the rate of severe IVH without
serious short-term gastrointestinal or renal adverse effects, a systematic review of
the literature reported no long-term beneficial effect on survival or
neurodevelopmental outcome [ 23 ].
Although vitamin E, a strong antioxidant, reduces the risk of IVH, especially severe
IVH, it is associated with an increased risk of sepsis particularly when given
intravenously to preterm infants [ 24 ].
MANAGEMENT OF IVH No specific therapy exists to limit the extent of IVH after it has
occurred. Treatment of IVH is supportive and directed towards preservation of cerebral
perfusion, minimization of any further brain injury, and early detection of IVH complications
[ 1 ].
Prevention of PHH Based on the assumption that PHH is primarily due to inflammatory
response of the subarachnoid villi to the presence of blood, the following proposed preventive
measures focused on removing blood products from the CSF. However, these interventions
have not been shown to be effective in preventing PHH.
Early lumbar puncture (LP) has been proposed as an intervention to try to reduce the
incidence of PHH by removing blood products from the CSF. A meta-analysis performed in
2000 demonstrated no difference in the outcomes of shunt placement, death, disability, and
multiple disabilities between repeated LPs and supportive measures alone [ 34 ]. However, it
is uncertain whether the published trials in this systematic review instituted interventions
early enough to be effective. In a subsequent observational study, patients who underwent
serial LPs performed early based on predetermined cranial ultrasound definition were less
likely to require shunt insertion than those treated late [ 35 ].
There also is a theoretical increased risk for CSF infection associated with repeat LPs. Further
evaluation including multicenter trials is needed to determine the efficacy and safety of serial
LPs in reducing clinically significant PHH.
Injection of fibrinolytic agents into the ventricular system of infants with IVH has been
suggested as an intervention to prevent PHH. However, there are mixed results in regards to
overall benefit, and there appear to be significant adverse events associated with fibrinolytic
therapy. As a result, fibrinolytic therapy for PHH should continue to be viewed as
experimental [ 36 ].
In a case-control study of 12 infants with PHH, there was no difference in the need
for shunt placement between infants who received intraventricular streptokinase
infusion compared to controls [ 37 ].
One trial (referred to as the DRIFT trial) in infants with PHH reported no difference in
the combined outcome of death and need for shunting between drainage,
irrigation, and fibrinolytic therapy with tPA (DRIFT therapy) and standard therapy
of serial taps of CSF from a ventricular reservoir (44 versus 50 percent) [ 38 ]. In
addition, patients who were treated with DRIFT intervention had an increased risk
of secondary IVH (12 of 34 infants versus 3 of 36). A subsequent report on the
two year outcomes showed decreased mortality, or risk of severe disability (54
versus 71 percent) and decreased severe cognitive disability (31 versus 59
percent) in the DRIFT group versus the control group [ 39 ]. There was no
difference in the incidence of sensorimotor disability.
Management of PHH Initial management of PHH is continued close surveillance and
detection of those infants who require intervention with rapidly progressing hydrocephalus
and increased ICP (algorithm 1 ). Ongoing monitoring involves weekly head ultrasounds
(with serial measurements of ventricular dimensions), daily recording of head circumference,
and frequent clinical assessment for signs of increased ICP.
In patients with rapid progression of PHH or in some patients with persistent slow
progression, the indications for intervention to manage hydrocephalus and prevent increased
ICP include [ 1 ]:
Serial lumbar punctures (LP) to drain CSF. Cranial ultrasonography before and after
LP may be needed to ensure that CSF removal leads to a decrease in ventricular
size, and that the ventricles do not return to either a similar or larger size too
quickly after the procedure is performed. If the LP does not arrest the progression,
more aggressive intervention such as ventricular drainage or shunting is needed.
Ventricular drainage is often used as a temporizing procedure to manage PHH in
infants who have not responded adequately to serial lumbar puncture and in
whom it is not feasible to perform a shunt procedure [ 43,44 ]. Some patients
treated with ventricular drainage will not require a permanent shunt. Drainage
procedures include:
Permanent ventricular shunt for continual CSF drainage cannot be performed if there
is excessive blood in the CSF and brain because blood may block the shunt and
cause increased ICP (hence the need for a temporizing drainage reservoir). The
most common shunts placed in premature infants are ventriculoperitoneal (VPS),
followed by ventriculosubgaleal and ventriculoatrial shunts. VPS is considered to
be the definitive treatment for PHH, but can be associated with significant
morbidity, especially in extremely premature and low birth weight infants.
Complications with shunts include infection, shunt blockage, and, with
ventriculosubgaleal and ventriculoatrial shunts, inadequate drainage. Endoscopic
ventriculostomy, particularly when accompanied by choroid plexus coagulation,
may be an effective treatment alternative to a VPS in some cases [48,49 ].
(See "Hydrocephalus", section on 'Shunt' and "Hydrocephalus", section on 'Third
ventriculostomy' .)
Although medications to reduce CSF production, such as acetazolamide and furosemide ,
have been used, there is no evidence that these medications are either effective or safe in
patients with PHH. In particular, there are no data that these agents decrease the need for
shunting or decrease mortality [36 ]. In fact, a meta-analysis of diuretic intervention studies
showed poorer outcome (including increased risk of motor impairment and nephrocalcinosis)
in treated infants [ 50 ].
Periventricular hemorrhagic infarction The pathogenesis of periventricular
hemorrhagic infarction (PHI) is thought to be infarction caused by venous obstruction after a
germinal matrix-intraventricular hemorrhage [ 28,51 ]. The circulatory disturbance occurs in
the subependymal region where the medullary veins drain into the terminal vein, as
demonstrated by Doppler ultrasound [ 52 ].
PHI most often involves the parietal and frontal cerebral areas, and in a quarter of patients,
PHIs are bilateral [ 53 ]. PHI results in the destruction of the motor and associative white
matter axons and evolves to a single or multiple cysts, which may become confluent with the
lateral ventricle [ 51 ]. PHI is manifested clinically by a spastic hemiparesis or an asymmetric
spastic quadriparesis that usually is accompanied by intellectual deficits.
Periventricular leukomalacia Periventricular leukomalacia (PVL) is the major form of
brain white matter injury in neonates, especially premature infants. It occurs in a
characteristic distribution and consists of periventricular focal necrosis and more diffuse
gliotic cerebral white matter injury. In the past, subsequent cystic formation that was large
enough to be detected by ultrasound was also commonly observed, but is less frequently
seen now. There is a strong association between PVL and IVH, with the two disorders often
occurring in the same patient. It is unknown whether there is a causal relationship or
whether the two entities develop in parallel because of common pathologic processes. There
are data to suggest that IVH may exacerbate PVL, due to the presence of non-protein-bound
iron in the CSF [ 28 ]. PVL is associated with the subsequent development of cerebral palsy,
intellectual impairment, and visual disturbances. PVL is discussed in greater detail separately.
(See"Periventricular leukomalacia" .)
OUTCOME
Mortality and short-term morbidity Mortality and short-term morbidity are closely
related to the severity of IVH.
In severe IVH (grades III and IV), the mortality rate is approximately 20 percent,
and 75 percent of the survivors develop posthemorrhagic hydrocephalus (PHH)
[ 1 ]. Severe IVH also increases the risk of subsequent development of
periventricular leukomalacia [ 54 ]. (See "Periventricular
leukomalacia" and 'Periventricular leukomalacia' above.)
For mild IVH (grades I and II), mortality drops to 5 percent, with only 7 percent of
survivors exhibiting PHH [ 26 ].
Long-term outcome The long-term outcome of infants who survive with IVH worsens
with increasing severity of IVH and decreasing gestational age. This is demonstrated in the
following studies:
ELBW infants with severe IVH who require shunt insertion for management of PHH
are at the greatest risk for adverse neurodevelopmental outcome. In a study from
the National Institute of Child Health and Human Developmental (NICHD)
Neonatal Research Network, poorer performance at 18 to 22 months on the
Bayley Mental and Psychomotor Developmental Indexes (MDI and PDI) was
observed for infants with grade III and IV IVH requiring shunt placement for PHH
when compared with those with grade III and IV IVH not requiring shunt
placement [ 59 ]. The mean MDIs were 74, 66, 71.5, and 60 for grade III without
shunt, grade III with shunt, grade IV without, and grade IV with shunt,
respectively; mean PDIs were 77, 64, 73, and 55 for grade III without shunt,
grade III with shunt, grade IV without, and grade IV with shunt, respectively. The
risk for CP also increased with the severity of IVH and need for shunt replacement
with a prevalence of CP of 23, 57, 37, and 80 percent for grade III without shunt,
grade III with shunt, grade IV without, and grade IV with shunt, respectively.
Even mild IVH (grades I and II) in ELBW infants is associated with neurodevelopmental
impairment. In a study of 104 ELBW infants with isolated grade I or II IVH and 258 control
infants without IVH, infants with IVH compared to those without had a lower mean MDI score
(74 versus 79) at twenty months corrected age [ 60 ]. After adjusting for confounding
factors, infants with mild IVH had a higher rate of MDI <70 (45 versus 25 percent), CP (13
versus 5 percent), and deafness (9 versus 2 percent) when compared with infants without
IVH.
However, it is likely that PVL is the major determinant of neurologic outcome rather than IVH
alone. The studies cited above do not necessarily define or add PVL as a predictive variable
separate from IVH. (See "Periventricular leukomalacia", section on 'Prognosis' .)
INFORMATION FOR PATIENTS UpToDate offers two types of patient education
materials, The Basics and Beyond the Basics. The Basics patient education pieces are
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patients who want a general overview and who prefer short, easy-to-read materials. Beyond
the Basics patient education pieces are longer, more sophisticated, and more detailed. These
articles are written at the 10 th to 12 th grade reading level and are best for patients who want
in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to
print or e-mail these topics to your patients. (You can also locate patient education articles
on a variety of subjects by searching on patient info and the keyword(s) of interest.)
Basics topics (see "Patient information: Intraventricular hemorrhage in newborns (The
Basics)" )
SUMMARY AND RECOMMENDATIONS Although intraventricular hemorrhage (IVH) is
an important cause of brain injury in premature infants, currently there is no specific therapy
to limit the extent of IVH after it has occurred or to prevent the complication of
posthemorrhagic hydrocephalus (PHH). Management is focused on prevention of IVH.
Because IVH is most common in premature infants, the most effective strategy to
prevent IVH is to reduce the incidence of preterm birth. When preterm birth
cannot be avoided, the following interventions are used to reduce the risk of IVH.
(See 'Prevention of IVH' above.)
General preventive neonatal care for preterm infants, based on the understanding of
the pathogenesis and risks factors for IVH, includes prompt and appropriate
efforts to avoid hemodynamic instability and metabolic derangements, provide
adequate cerebral perfusion and oxygenation, and correct coagulation
abnormalities. (See 'General neonatal care' above.)