Management and complications of intraventricular hemorrhage in the newborn

Management and complications of intraventricular hemorrhage in the newbornAuthor   Lisa M Adcock, MD   Section Editors   Douglas R Nordli, Jr, MD   Joseph A Garcia-Prats, MD   Deputy Editor   Melanie S Kim, MD   DisclosuresAll topics are updated as new evidence becomes available and our peer review process   is complete.Literature review current through: Oct 2013. | This topic last updated: Feb 1, 2013.

INTRODUCTION  — Intraventricular hemorrhage (IVH) (also known as subependymal/intraventricularhemorrhage) is an important cause of brain injury in premature infants. The negative impact of IVH on neurodevelopmental outcome is due not only to the direct consequences of IVH, but also to associated lesions, such as posthemorrhagic hydrocephalus and periventricular leukomalacia.

Although the incidence of IVH in very low birth weight (VLBW) infants with birth weights <1500g has declined from rates as high as 40 to 50 percent in the late 1970s to 20 to 25 percent in 2010, the absolute numbers of infants with IVH remain significant. This is due to the increased survival rate of premature infants, especially in the extremely low birthweight (ELBW) category (birth weight below 1000 g) who continue to be at risk for IVH [ 1,2   ]. (See "Clinical manifestations and diagnosis of intraventricular hemorrhage in the newborn", section on 'Epidemiology'   .)

The prevention, management, complications, and outcome of IVH in the premature newborn are discussed in this topic review. The epidemiology, pathogenesis, clinical manifestations, and diagnosis of IVH are discussed separately. (See "Clinical manifestations and diagnosis of intraventricular hemorrhage in the newborn"   .)

SEVERITY OF IVH AND GRADING  — The severity of IVH is based on the presence and amount of blood in the germinal matrix and lateral ventricles as demonstrated by cranial ultrasound ( table 1   ):

Grade I: Only germinal matrix hemorrhage. Grade II: Intraventricular hemorrhage involving 10 to 50 percent of the ventricular

area.

Grade III: Intraventricular hemorrhage involving more than 50 percent of the ventricular area.

Grade IV has traditionally been defined as hemorrhage in any parenchymal location in addition to a unilateral or bilateral IVH [ 3   ]. Others have suggested that periventricular density (including parenchymal hemorrhage) be described specifically regarding size and location rather than be incorporated into the grading system [ 4   ].

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.

Antenatal corticosteroids – A systematic meta-analysis demonstrated antenatal corticosteroids given before preterm birth reduced the risk of IVH detected by ultrasound examination (OR 0.29, 95% CI 0.14 to 0.61) [ 5   ]. (See "Antenatal corticosteroid therapy for reduction of neonatal morbidity and mortality from preterm delivery"   .)

Delayed clamping of the umbilical cord (>30 seconds) – A systematic meta-analysis demonstrated a lower relative risk of IVH in infants with delayed versus early clamping of the umbilical cord (RR 0.56, 95% CI 0.36 to 0.93) [ 6   ]. 

In a subsequent trial of 72 preterm infants (gestational age less than 32 weeks), the rate of IVH was lower in infants who were randomly assigned to delayed versus early cord clamping (9 versus 42 percent) [ 7   ]. (See "Management of normal labor and delivery", section on 'Cord clamping'   .)

Maternal transport – Premature infants whose mothers were transported to a perinatal center prior to delivery are less likely to have IVH than similar infants who are transported after delivery. This was illustrated in an analysis of the United States National Inpatient Database of very low birth weight (VLBW) infants (birth weight <1500 g) born between 1997 and 2004 [ 8   ]. In this review, inborn patients compared to those who were transported had a lower incidence of IVH (13.2 versus 27.4 percent). In patients with IVH, the relative distribution of severe IVH was lower in the inborn group compared to the transported group (32.9 versus 44.1 percent).

Delivery mode does not appear to affect the risk of severe IVH. This was illustrated in a review of the Israel National Very Low Birth Weight (VLBW) Infant database that included 4658 infants born between 1995 and 2004, which demonstrated no difference in the incidence of severe IVH between infants born by vaginal versus cesarean delivery when confounding factors were controlled [ 9   ].

For infants born by cesarean delivery, data are conflicting on whether the presence or absence of labor affects the risk of severe 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'   .)

Prompt and appropriate resuscitation including efforts to avoid hemodynamic instability or conditions that impair cerebrovascular autoregulation, such as hypoxia, hypercarbia, hyperoxia, and hypocarbia.

Hypotension and hypertension should be avoided, and if present, corrected. In a randomized trial that compared minimal to routine handling of premature infants, elevations of systemic blood pressure that occurred during intensive care procedures or spontaneous motor activity were associated with IVH [ 12,13   ]. 

Although hemodynamic instability needs to be treated in a timely fashion, large acute changes in blood pressure, which may occur with large bolus infusions of parenteral fluid, should be avoided when treating hypotension.

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'   .)

Abnormalities in coagulation should be corrected [ 14   ]. (See "Disseminated intravascular coagulation in infants and children", section on 'Treatment'   and "Neonatal thrombocytopenia", section on 'Platelet transfusion'   .) 

Research has focused on interventions that reduce the risk of bleeding to prevent IVH, such as fresh frozen plasma and ethamsylate.

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.

A systematic meta-analysis demonstrated that treatment with ethamsylate compared to placebo decreased the risk of IVH in preterm infants less than 31 weeks gestation (RR 0.63, 95% CI 0.47-0.86). The risk of severe IVH was lower in infants less than 35 weeks gestation (RR: 0.67, 95% 0.49-94) but not in the subgroup of infants below 32 weeks gestation [ 15   ]. There were no differences between the two ethamsylate and placebo groups in mortality and developmental outcome at two years of age. There were no identified adverse effects associated with ethamsylate. However, we do not recommend the routine prophylactic use of ethamsylate because currently available data do not demonstrate long-term benefit in infants less than 32 weeks gestation (most at-risk group).

Consideration should be given to treating asymptomatic patent ductus arteriosus (PDA) because the incidence of IVH is greater in preterm infants with PDA compared to those without a PDA [ 16]. (See "Pathophysiology, clinical manifestations, and diagnosis of patent ductus arteriosus in premature infants", section on 'Systemic and cerebral blood flow effects'   .)

Ineffective interventions  — We do not recommend the routine use of interventions that are ineffective in preventing IVH, do not demonstrate long-term benefit, or are associated with significant adverse outcomes.

Ineffective therapies for prevention of IVH include:

Phenobarbital   — Antenatal administration of phenobarbital to women in preterm labor did not reduce the risk of intracranial hemorrhage or early death compared to controls (23 percent in each group) [ 17   ]. Postnatal administration of phenobarbital also does not appear to prevent IVH in premature infants. In a systematic review, postnatal administration of phenobarbital did not reduce the rate of IVH, severe IVH, neurologic impairment, ventricular enlargement, or death, and was associated with increased need for mechanical ventilation [ 18   ].

Antenatal vitamin K — Administration of vitamin K to the mother prior to very premature birth does not appear to significantly prevent IVH. In a systematic review of five trials, antenatal vitamin K failed to prevent IVH [ 19   ].

Postnatal ibuprofen   — In a controlled trial in which 415 premature infants (gestational age <31 weeks) were randomly assigned to prophylactic administration of ibuprofen or placebo (within six hours of birth), administration of ibuprofen did not reduce the frequency of severe IVH (8 to 9 percent in both groups) [ 20   ]. Another

randomized trial of 155 premature infants (<28 weeks gestation) documented IVH (grades II to IV) in 16 percent of ibuprofen-treated infants versus 13 percent of placebo-treated infants [ 21   ]. A third randomized trial of infants <28 weeks gestation reported a decrease in the rate of severe IVH (23 to 11 percent), but did not show improved survival in infants treated with prophylactic ibuprofen compared with control patients. Ibuprofen was also associated with a higher frequency of serious adverse events (including severe hypoxemia, necrotizing enterocolitis, intestinal perforation, oliguria, pulmonary hypertension, and elevated creatinine) [ 22   ]. The trial was prematurely terminated because of three cases of severe pulmonary hypertension in the ibuprofen group.

Antenatal administration of magnesium sulfate   – A systematic meta-analysis demonstrated no benefit in the administration of magnesium sulfate in the reduction of IVH [ 1   ].

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   ].

General measures include the following:

Maintenance of arterial perfusion to avoid hypotension or hypertension and preserve cerebral blood flow

Adequate oxygenation and ventilation with specific avoidance of hypocarbia, hypercarbia, and acidosis

Provision of appropriate fluid, metabolic, and nutritional support

Seizures should be treated to avoid any associated impairment of cerebral oxygenation, cerebral perfusion, or systemic blood pressure.

Detection of posthemorrhagic hydrocephalus (PHH), the major complication of IVH. Weekly head ultrasound is the most important monitoring tool because serial studies can detect early asymptomatic PHH. Other assessment measures include daily head measurement (although rapid head growth usually occurs late in the course of PHH) and monitoring for signs and symptoms of increased intracranial pressure (which are relatively uncommon in affected neonates). (See"Elevated intracranial pressure in children"   .)

An observational study reported recombinant erythropoietin (rEPO) appeared to have a neuroprotective effect in infants with IVH [ 25   ]. In this cohort of ELBW infants, patients who received rEPO in the first few weeks of life had better IQ scores on cognitive testing than those not treated with rEPO when evaluated at 10 to 13 years of age. However, clinical trials confirming the long-term benefit are needed before rEPO can be recommended as routine therapy for patients with IVH.

COMPLICATIONS  — Posthemorrhagic hydrocephalus, periventricular hemorrhagic infarction, and periventricular leukomalacia are major sequelae of IVH.

Posthemorrhagic hydrocephalus (PHH)  — Posthemorrhagic hydrocephalus (PHH), also referred to as progressive ventricular dilatation (PVD), occurs in approximately 25 percent of

infants with IVH [ 26]. PHH usually begins within one to three weeks after IVH. However, the clinical presentation of increasing head circumference and signs of increased intracranial pressure (ICP) occurs late in the course and usually presents days to weeks after ventricular dilation is detected by brain imaging studies ( image 1   and image 2   ) [ 27   ].

Both mortality rate and poor developmental outcome are greater in patients who develop PHH compared to those without PHH. The deleterious effects of PHH are thought to be caused by injury to the periventricular white matter that results in cystic or diffuse periventricular leukomalacia [ 28   ]. PHH appears to be a more common complication of severe IVH than mild IVH, as only 7 percent of patients with grades I and II IVH exhibit progressive VD compared to 70 to 75 percent of patients with grades III and IV IVH [ 1   ]. In addition, the rate of progression is faster and the likelihood of spontaneous arrest lower in patients with severe IVH (See 'Periventricular leukomalacia'   below and 'Outcome'   below and "Periventricular leukomalacia", section on 'Pathophysiology'   .)

In the majority of PHH cases, hydrocephalus is thought to be caused by impaired reabsorption of the cerebrospinal fluid (CSF) due to inflammation of the subarachnoid villi by blood [ 1,29   ]. Transforming growth factor beta (TGF-B), one of the inflammatory factors, stimulates the production of extracellular matrix, which causes scarring and obstruction of arachnoid villi [ 30-33   ]. This results in communicating hydrocephalus, in which the entire ventricular system is dilated. Less frequently, patients can have noncommunicating hydrocephalus due to obstruction by a clot or scarring within the ventricular system.

PHH needs to be differentiated from nonprogressive ventricular dilation, also referred to as stable ventriculomegaly or stable ventricular dilation, due to cerebral atrophy, as the approach to management between the two entities differs. Stable ventricular dilatation occurs in 25 percent of patients with IVH. In addition, some degree of cerebral atrophy may also be present in patients with PHH [ 26   ].

The risk of PHH increases with increasing size of IVH, decreasing gestational age, and greater severity of illness [ 1,26   ].

There are three different clinical courses of PHH [ 1,26   ]:

Spontaneous arrest without a need for intervention (40 percent) Rapid progression (10 percent)

Persistent slow progression (50 percent), in which 20 percent arrest after intervention but without shunting, and 30 percent require shunting

An additional 5 percent of infants with spontaneous or treatment-associated arrest of PHH will develop late progression of their disease in the newborn period or, rarely, after discharge from the NICU in the first year of life.

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   ]:

Cranial ultrasound that demonstrates significant lateral ventricular dilation. Many centers use the Levene definition of dilated ventricles of greater than 4 mm above the 97 th percentiles for postmenstrual age [ 40,41   ].

Clinical evidence of increased ICP with a bulging fontanelle or splayed cranial sutures. Opening pressures greater than 80 mm H20 in preterm infants can be used as an indication of increased ICP and decreased cerebral compliance. Doppler measurement of the resistive index (RI) before and after external compression of the anterior fontanelle by the ultrasonic transducer is another way to measure cerebral compliance. Infants with PHH requiring a shunt have a greater change in RI than those with arrested PHH [ 42   ].

Increase in head circumference that exceeds 2 cm/week.

Interventions to manage progressive PHH include [ 1,36   ]:

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:

Direct external ventricular drain

Tunneled subcutaneous ventricular drain to an external drip chamber

Tunneled subcutaneous ventricular drain to a subcutaneous reservoir, which can be tapped for CSF removal. In variations of this system, the tunneled catheter drains into a surgically prepared pouch in the supraclavicular region or subgaleal space [ 45-47   ]. A subgaleal shunt may function as a continuous drain and not require tapping unless drainage is inadequate or shunt obstructs distally.  

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:

The neurodevelopmental outcomes of 270 ELBW infants were evaluated at eight years of life. The prevalence of cerebral palsy (CP), major neurosensory disability, and cognitive dysfunction increased with the presence and the severity of IVH [ 55   ]. The most adversely affected patients were the six individuals who had grade IV IVH.

In another study, 575 infants were identified with IVH from 1981 to 1999 in a single center [ 56]. There were 160 deaths during birth hospitalization including 80 infants with grade IV IVH. Of the survivors, 335 patients (with a mean birth weight of 1162 gm and gestational age of 28 weeks) were evaluated at a mean follow-up age of 7.5 years (range 3 to 20 years). The neurodevelopmental outcomes were normal in 56 percent of the survivors. Adverse outcomes included CP, intellectual disability (mental retardation), and borderline intelligence in 22, 10, and 11 percent of patients, respectively. Only 8 of the 52 patients with grade IV IVH (15 percent) had normal outcomes compared to 87 of 124 with grade I IVH (70 percent). The risk of grade IV IVH and poorer neurodevelopmental outcome increased with decreasing gestational age and birth weight.

In the Indomethacin   Intraventricular Hemorrhage (IVH) Prevention Trial, preterm survivors with severe brain injury (defined as grade III or IV IVH, periventricular leukomalacia, or severeventriculomegaly/hydrocephalus) were more likely to require additional school services and have lower IQ scores than survivors with normal head imaging at 12 years of age [ 57   ].

In a population-based prospective study of 1812 infants born before 33 weeks gestation, the prevalence of CP at five years of age increased with worsening neonatal IVH. CP was diagnosed at five years of age in 8 percent of survivors with grade I IVH, 11 percent in grade II, 19 percent in grade III, and 50 percent in grade IV [ 58   ].

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'   .)

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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.)

In mothers who are at risk for preterm delivery, we recommend administration of antenatal corticosteroids ( Grade 1B   ).

During the delivery of preterm infants, we recommend delayed clamping of the umbilical cord (Grade 1B   ).

We recommend transfer of mothers in preterm labor to a perinatal center with experience in high-risk deliveries and care of preterm infants ( Grade 1B   ).

We suggest NOT performing early lumbar punctures in an effort to prevent PHH because studies do not demonstrate any benefit compared to supportive care ( Grade 2B   ).

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.)

We recommend NOT administrating the following medications that do not appear beneficial in preventing IVH, or have unacceptable adverse effects: antenatal phenobarbital   , antenatal vitamin K, and the postnatal administration of indomethacin   , ibuprofen   , phenobarbital, and vitamin E (Grade 1B   ). (See 'Ineffective interventions'   above.)

In neonates with IVH, management is supportive and focused on reducing further brain injury through preservation of cerebral perfusion and oxygenation by maintaining mean arterial perfusion and adequate oxygenation and ventilation, and providing appropriate fluid, metabolic, and nutritional support. In addition, seizures are treated in a timely manner to avoid hypoxia or hypotension. Ongoing surveillance that includes daily head measurement, weekly brain imaging (image 1   and image 2   ), and monitoring for signs of increased intracranial pressure (ICP) are used for early detection of PHH. (See 'Management of IVH'   above.)

Complications of IVH include PHH, periventricular hemorrhagic infarction, and periventricular leukomalacia. PHH, the most common complication, occurs in approximately 25 percent of infants with IVH. The incidence of PHH increases with

the severity of IVH. In 60 percent of infants with PHH, intervention is required to avoid increasing ventricular dilation and increased ICP. (See'Complications'   above.)

Infants with rapid progression of hydrocephalus or with signs of increased ICP require neurosurgical intervention. In these patients with PHH, we do NOT recommend treatment withacetazolamide   or furosemide   , since studies document no improvement in outcome and, in some cases, worsening of outcome ( Grade 1B   ). (See 'Management of PHH'   above and "Hydrocephalus".)

Increased severity of IVH is associated with increased mortality and morbidity. Mortality rate is approximately 20 percent in infants with severe IVH (grades III and IV) ( table 1   ), and up to 75 percent of the survivors develop PHH. (See 'Outcome'   above.)