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Neonatal cerebellar hemorrhage

Neonatal cerebellar hemorrhage
Literature review current through: Jan 2024.
This topic last updated: May 02, 2023.

INTRODUCTION — Cerebellar hemorrhage (CBH) is the major and most frequent cause of neonatal cerebellar injury in very preterm infants (gestational age <32 weeks). Infants with extensive cerebellar lesions are at risk for poor outcome with decreased survival. In preterm survivors less severe bleeds are also associated with significant long-term neurodevelopmental impairment.

The risk factors, presentation, management, and outcome of neonatal cerebellar hemorrhage will be discussed here. An overview of cerebellar development and cerebellar disorders is presented separately. (See "Overview of cerebellar injury and malformations in neonates".)

PATHOLOGY AND PATHOGENESIS

Preterm infants — In very preterm infants (gestational age [GA] <32 weeks), there is a wide range of pathology due to CBH, ranging from small punctate lesions detected by magnetic resonance imaging (MRI), focal unilateral bleeds, and massive bleeds involving both hemispheres and including the vermis [1].

Traditionally, two pathologic patterns of preterm CBH were described. The first consists of extensive CBH occurring in the sickest and most immature infants (<28 weeks gestation and/or <750 g) (image 1) [2,3]. These large lesions often lead to a destruction of cerebellar parenchyma and subsequent volume reduction and are associated with long-term neurodevelopmental disabilities in surviving infants [4]. The second pattern includes single or multiple small, punctate (<3 to 4 mm) hemorrhages detected by MRI (image 2). These small lesions are usually not detected by cranial ultrasound and are frequently encountered as a chance finding on MRI. They usually do not lead to cerebellar volume reduction and are associated with a more favorable prognosis [5,6].

In more recent studies, a third category of limited/focal lesions (ie, larger than punctate hemorrhages but smaller than the extensive CBH) has been described [4]. Outcomes tend to be more favorable with these lesions than in cases with extensive CBH, but this also depends on size/location and additional complications. (See 'Outcome' below.)

Neuroimaging studies show that most affected preterm survivors have unilateral lesions, whereas bilateral hemorrhage is predominately seen in autopsy cases [1]. In the majority of cases, hemorrhage occurs in the lateral or in the inferior part of the posterior lobe in the region supplied by the posterior inferior cerebellar artery (image 3). Smaller "satellite" lesions are often associated with larger lesions.

Microscopically, large hemorrhages involve the cortex near the junction of the white matter and the internal granular layer and/or adjacent white matter [1]. (See "Overview of cerebellar injury and malformations in neonates", section on 'Development'.)

Severity and grading — In preterm infants with CBH, the location and extent of the lesion(s) are important to neurodevelopmental outcome. Classification systems have been proposed based on neuroimaging studies and extend beyond the traditional two pathologic patterns described above. The severity of CBH is based on the size of the lesion, the location including unilateral or bilateral involvement and involvement of the vermis and the degree of cerebellar volume loss at term equivalent age [4,7-10].

The authors have previously developed and used the following classification to grade severity of CBH for both ultrasound and MRI for preterm infants during the preterm period and at term equivalent age, which has been correlated with neurodevelopmental outcome [4,8]. Within this classification, a distinction is made between punctate and larger hemorrhages, and the larger cerebellar lesions are further divided into limited and extensive. The latter distinction is important as infants with limited CBH have a better prognosis than infants with extensive CBH [4].

The following grading categories are used (table 1) [8]:

Grade 0 – Normal echogenicity (ultrasound)/signal intensity (MRI) of the cerebellar vermis and hemispheres with normal anatomic features. No signs of destruction or atrophy.

Grade 1 – Small (<4 mm) focal, punctate lesion(s) in the cerebellar parenchyma. These punctate lesions are usually not detected by ultrasound but are a frequent finding on MRI performed in preterm infants. There is usually no atrophy on follow-up ultrasound or MRI (image 4).

Grade 2 – Limited CBH, larger than a punctate lesion (≥4 mm) but involving at the most one-third of a single cerebellar hemisphere. Usually, these lesions involve the lateral or inferior convexity of the cerebellar hemisphere(s). They can be detected by cranial ultrasound, especially when mastoid fontanel views are performed. On follow-up scans, focal cystic degeneration or atrophy may be seen, involving again at the most one-third of the affected cerebellar hemisphere (image 3 and image 5).

Grade 3 – Extensive CBH, involving more than one-third of the cerebellar hemisphere. These lesions lead to obvious volume reduction of the cerebellar hemisphere on follow-up imaging (image 1 and image 6).

Each grade of CBH can be unilateral or bilateral and either symmetric or asymmetric. Involvement of the vermis (isolated or in combination with cerebellar hemispheric lesions) is noted separately.

An alternative classification system categorizes MRI signal abnormalities in the cerebellum at term equivalent age into four grades depending on size (either small (≤3 mm) or large (>3 mm) and location [uni- or bilateral involvement]). It also categorizes cerebellar volume reduction at term equivalent age into three different categories according to the transcerebellar diameter (TCD), corrected for age at scanning (normal cTCD ≥50 mm) (image 7) [9].

In some studies, volumetric MRI has been used to quantify the overall burden of cerebellar lesions, and both the total volume and location of the lesions was associated with outcome [11]. (See 'Neurodevelopmental outcome' below.)

Pathogenesis — Supratentorial germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH) is frequently observed in neonates with CBH (in 95 percent of autopsy cases and in 65 to 80 percent of survivors based on neuroimaging studies [3,7]) suggesting a common underlying pathogenesis [1,12]. In both conditions, bleeding occurs in highly fragile cellular and vascular developing regions of the brain (external and internal granular cell layer for the developing cerebellum [CBH] and the supratentorial germinal matrix layer under the ependymal lining of the ventricles [GMH-IVH]). During this period, acute fluctuations of arterial blood flow due to impaired cerebral blood flow auto-regulation in these fragile, highly vascular networks contribute to capillary damage, resulting in bleeding observed in preterm infants with CBH and GMH-IVH. (See "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in the newborn: Risk factors, clinical features, screening, and diagnosis", section on 'Pathogenesis'.)

CBH in preterm infants may disrupt the normal development of the cerebellum during a critical time of rapid and enhanced proliferation and differentiation [1,12]. Large CBH are often followed by cerebellar atrophy with a loss of cerebellar volume on magnetic resonance imaging [1,13,14]. This atrophy is generally focal in unilateral lesions and extensive in bilateral lesions and may need to be distinguished from cases of primary hypoplasia (image 1) [15]. (See "Overview of cerebellar injury and malformations in neonates".)

Late preterm and term infants — In late preterm (gestational age 34 to <37 weeks) and term infants, massive posterior fossa hemorrhage is mostly related to birth trauma due to direct laceration of the cerebellum or the tentorium or to rupture of cerebellar bridging veins or the occipital sinus (image 8) [16-18].

In addition, CBH has been observed in infants with perinatal asphyxia and those who undergo major surgery or were treated with extracorporeal membrane oxygenation [19-22]. In these cases, lesions may vary in size and are thought to be due to hemodynamic instability resulting in abrupt changes in perfusion of the cerebellum.

EPIDEMIOLOGY — The incidence of CBH increases with decreasing gestational age (GA).

Preterm infants — The incidence of CBH in preterm infants reported in studies varies widely, mainly due to differences in GA of studied infants and imaging techniques applied. The youngest and smallest infants are at greatest risk to develop CBH [2]. In addition, magnetic resonance imaging (MRI) is more sensitive than cranial ultrasound in detecting CBH and has increased the reported incidence with identification of small (punctate) lesions not detected by ultrasound. (See "Overview of cerebellar injury and malformations in neonates", section on 'Neuroimaging'.)

MRI – Several studies in very preterm infants (gestational age [GA] <32 weeks) reported incidences of CBH between 8 to 24 percent for infants undergoing routine MRI scans around term equivalent age [3,7,9,10]. One study reported a higher incidence of 37 percent in 73 preterm infants (GA <33 weeks) who were scanned shortly after birth (mean postmenstrual age of 32.4 weeks) with high resolution 3T-MRI and specific susceptibility MRI sequences for cerebellar hemorrhage [23]. (See 'Magnetic resonance imaging (MRI)' below.)

Cranial ultrasound using mastoid fontanel views – The reported incidence of CBH on cranial ultrasound using mastoid fontanel (MF) views in addition to the traditional anterior fontanel ranges from 3 to 9 percent in infants born below 32 weeks gestation and/or with a birth weight <1500 g [2,3,7,24,25]. MF views improve the visualization of the posterior fossa. (See 'Cranial ultrasound' below and "Overview of cerebellar injury and malformations in neonates", section on 'Cranial ultrasound'.)

In these studies, the largest and most destructive hemorrhages were especially common in extremely preterm (GA <25 weeks) and/or extremely low birth weight (<750 g) infants, in whom the incidence was as high as 15 percent (image 6 and image 1) [2,24].

The increased incidence of massive hemorrhage in extremely preterm infants was also shown by autopsy studies [26-28]. In one study, CBH on postmortem examination was seen in 20 percent of infants below 28 weeks gestation and 7 percent of infants born between 28 and 32 weeks gestation [26].

Term infants — The incidence of cerebellar injury in term infants is difficult to estimate, as these infants do not routinely undergo neuroimaging. However, it is likely that cerebellar injury has been underdiagnosed, as these lesions are increasingly reported in full term infants due to traumatic delivery (image 8), hypoxic-ischemic encephalopathy, and those undergoing neonatal surgery for both cardiac and noncardiac anomalies [19-22].

RISK FACTORS — CBH occurs most frequently in extremely preterm infants; the pathogenesis of CBH is multifactorial and includes maternal, peripartum, and early postnatal hemodynamic risk factors [29].

Risk factors for preterm infants — The risk of CBH and its long-term effect on neurodevelopment increases with decreasing gestational age. As discussed above, the fragility of the developing cerebellum and immaturity in auto-regulating cerebral blood flow increase the risk of CBH in preterm infants. In addition, injury disrupts the normal development of the cerebellum, which is critical and rapid throughout the last trimester of pregnancy and continues postnatally. (See 'Preterm infants' above and "Overview of cerebellar injury and malformations in neonates", section on 'Development' and "Overview of cerebellar injury and malformations in neonates", section on 'Prematurity and risk of cerebellar injury'.)

Very preterm infants (gestational age [GA] <32 weeks) and especially extremely preterm infants (GA <28 weeks) are also more likely to be severely ill with concomitant conditions that result in additional hemodynamic disturbances, which contribute to CBH [29]. The following have been associated with an increased risk of CBH in preterm infants presumably due to their negative effects on hemodynamic stability [2,5,10,23-25,29,30]:

Systemic hypotension with poor perfusion (ie, neonatal shock) requiring fluid resuscitation or the use of ionotropic agents. In a meta-analysis, systemic hypotension increased the odds of CBH by greater than five-fold (odds ratio 5.78, 95% CI 4.04-8.29) [29]. (See "Neonatal shock: Management", section on 'Initial stabilization'.)

Patent ductus arterious. (See "Patent ductus arteriosus (PDA) in preterm infants: Clinical features and diagnosis", section on 'Consequences of a PDA'.)

Respiratory failure requiring intubation and mechanical ventilation.

Acidosis based on a low pH in the early neonatal period.

Perinatal asphyxia.

In contrast, antenatal administration of magnesium sulphate, which appears to stabilize the cerebral circulation by reducing blood pressure fluctuations, demonstrates a neuroprotective effect with a decreased risk of both CBH and cerebral palsy [23,31]. (See "Neuroprotective effects of in utero exposure to magnesium sulfate" and 'Prevention' below.)

Although several studies suggested that antenatal corticosteroids reduced the risk of neonatal cerebellar injury [10,25,30], a subsequent meta-analysis did not find any association between antenatal corticosteroids and CBH [29].

Risk factors for term infants — Reported risk factors for CBH for term infants include [17,19,20,22,32]:

Birth trauma – Peripartum risk factors contributing to a complicated delivery include a primiparous mother, a large fetal head and/or small birth canal, breech presentation, forceps-assisted delivery, and prolonged labor. In these settings, there can be an increase in cerebral venous pressure and severe distortion and rupture of large cerebral veins (image 8). Direct traumatic cerebellar laceration and contusions due to occipital osteodiastasis may also occur [19].

Perinatal asphyxia ‒ Evidence of perinatal asphyxia or distress, including fetal heart rate abnormalities, need for emergency cesarean section, and required resuscitation in the delivery room.

Perinatal infection ‒ In one cohort study, one-third of the infants had mothers who were positive for group B streptococcus (GBS), although none of the newborn infants had GBS infection [19].

Unproven risk factor — In the previously mentioned systematic review, no association was observed between CBH and maternal age, chorioamnionitis, pre-eclampsia or multiple pregnancy in preterm infants [29]. It is also unclear whether coagulopathy and thrombocytopenia contribute to an increased risk of CBH and if correction of coagulopathy and thrombocytopenia reduces the risk of CBH. Data are also insufficient to determine whether coagulopathy and thrombocytopenia are risk factors for germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH). (See "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in the newborn: Risk factors, clinical features, screening, and diagnosis", section on 'Postnatal factors'.)

PRESENTATION

Prenatal presentation — Advances in prenatal ultrasound and the use of fetal magnetic resonance imaging (MRI) have led to increased recognition of CBH in high-risk fetuses (see "Prenatal diagnosis of CNS anomalies other than neural tube defects and ventriculomegaly", section on 'Posterior fossa abnormalities'). These lesions have been associated with congenital infection, hydrops fetalis, anemia, and intrauterine transfusion, and with maternal conditions such as sepsis, preeclampsia, trauma, and coagulation disorder [33-36]. Still, fetal CBH is a relatively rare event, and the majority of reports were described after termination of pregnancy or fetal demise.

When CBH occurs antenatally, it may lead to a disruption of further cerebellar development. After birth, fetal CBH may present as either uni- or bilateral cerebellar hypoplasia and mimic cerebellar malformation [37]. In a series of 26 fetuses with unilateral cerebellar hypoplasia diagnosed at a mean GA of 26 weeks, in eight cases, the progression of imaging features on fetal ultrasound and/or MRI were highly suggestive of an ischemic or hemorrhagic insult [38]. Other case reports described similar findings of antenatal cerebellar injury presenting as cerebellar hypoplasia or malformation after birth [33,35,39-41].

On prenatal ultrasound, CBH presents as a hyperechogenic intraparenchymal lesion, often rapidly evolving to a hypoechogenic lesion in the subacute phase (image 9). Hemosiderin staining can be recognized on susceptibility-weighted and/or T2* echo gradient MRI sequences obtained pre- or postnatally.

Postnatal presentation of preterm infants — CBH can have different presentations in the preterm infant depending on the size and acuteness of the lesion. Like GMH-IVH (see "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in the newborn: Risk factors, clinical features, screening, and diagnosis", section on 'Postnatal factors'), most CBH occur during the first postnatal week. However, especially in extremely preterm (gestational age <28 weeks) and preterm infants with intrauterine growth restriction, CBH may develop later during the neonatal period around episodes of respiratory and/or circulatory failure and/or sepsis.

Catastrophic presentation ‒ Uncommonly, infants with CBH present with catastrophic deterioration. These patients typically also have supratentorial hemorrhage (GMH-IVH) (image 10) [26,27]. Findings include stupor/coma, irregular respirations with hypoventilation or apnea, decerebrate posturing, bradycardia, and/or seizures. These infants may die within 12 to 36 hours after the initial onset of deterioration. The diagnosis of CBH as well as GMH-IVH is made by cranial ultrasound. (See "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in the newborn: Risk factors, clinical features, screening, and diagnosis", section on 'Clinical features'.)

Detection by neuroimaging screening ‒ In very preterm infants at-risk for CBH (gestational age <32 weeks), neuroimaging screening will detect CBH in asymptomatic patients or those with nonspecific findings, such as apnea or motor agitation [42,43]. These cases are generally detected by ultrasound screening of the posterior fossa using mastoid fontanel views or by MRI performed for various indications during the neonatal period or because of neurodevelopmental sequelae in later life [44,45]. (See 'Cranial ultrasound' below and 'Diagnosis' below.)

Non-catastrophic signs of CBH are nonspecific and include unexplained motor agitation, which may precede evidence of hemorrhage, and/or unexplained ventriculomegaly (ie, no evidence of significant supratentorial injury or congenital CNS abnormalities) on routine cranial ultrasound scans [43]. CBH can cause ventricular dilatation by either acute compression of the fourth ventricle or by extension of hemorrhage into the fourth ventricle and/or subarachnoid space, impeding cerebrospinal fluid circulation and reabsorption. Both unexplained ventricular dilatation and motor agitation are indications to perform targeted ultrasound screening, using the mastoid fontanel, as this will detect the majority of clinically significant CBH [2,3,7,46,47]. (See 'Cranial ultrasound' below and "Overview of cerebellar injury and malformations in neonates", section on 'Cranial ultrasound'.)

Postnatal presentation of term infants — Full-term infants with CBH may present with non-specific findings of irritability, apnea and/or seizures, often shortly after birth [19]. Some infants will present with acute catastrophic deterioration following birth trauma, mainly when CBH occurs in combination with large extra-axial posterior fossa hemorrhage [19]. (See 'Risk factors for term infants' above.)

Ultrasound should be performed in all infants with unexplained neurologic symptoms and/or severe illness to avoid a delay in diagnosis because the findings of CBH are nonspecific. Ultrasound findings that are suggestive of posterior fossa hemorrhage are ventriculomegaly in absence of GMH-IVH, (asymmetric) elevation of the tentorium, loss of normal demarcation of the posterior fossa structures, increased echogenicity within of one or both cerebellar hemispheres, and, rarely, herniation of the cerebellar tonsils into the foramen magnum or upwards transtentorial herniation of posterior fossa structures [18,48].

Data are limited to small case series. In one study of 20 term infants with CBH, the presenting signs included apnea in 14 patients occurring within 12 hours of birth and six presented with seizures within 36 hours of birth [19]. Lesions were small (<1 cm) in 12 cases, and large in eight cases. Primiparity was observed in half of the mothers, and the following were noted in one-third of cases: advanced maternal age, group B streptococcus-positive mothers, abnormal fetal heart rate, and instrumented delivery. Neurosurgical intervention was required in 5 out of 20 infants (25 percent); three required hematoma evacuation, and two others ventricular peritoneal shunts. Those infants who developed apnea, seizures, or required neurosurgical intervention all had cerebellar lesions >1 cm in size.

NEUROIMAGING

Cranial ultrasound — In our neonatal intensive care units, routine screening cranial ultrasound examinations are performed in all very preterm infants (gestational age <32 weeks) to detect supratentorial hemorrhage (ie, GMH/IVH), CBH, white matter injury and other brain abnormalities. During the first postnatal week at least one of the routine ultrasound scans is performed including mastoid fontanel windows, and subsequent serial ultrasound examinations using the mastoid fontanel window are performed on a regular basis in extreme preterm infants after the first postnatal week. Mastoid fontanel views provide better visualization of the posterior fossa than the traditional routine anterior fontanel window (figure 1) [8,47]. Mastoid fontanel images of the posterior fossa are performed in transverse planes while scanning from superior to inferior and in coronal planes scanning from anterior to posterior. The brain stem, cerebellar hemispheres, vermis, fourth ventricle, and cisterna magna can be visualized by this approach, and the transcerebellar diameter (TCD) can be measured to monitor cerebellar growth (image 7 and image 11 and image 12) [47,49-51]. An alternative approach to monitor cerebellar growth is transnuchal ultrasound using the foramen magnum [52]. (See "Overview of cerebellar injury and malformations in neonates", section on 'Cranial ultrasound'.)

CBH has a variable ultrasound appearance, depending on the timing of the examination [8]. In the acute stage, an area of increased echogenicity is seen within the cerebellar parenchyma. In the subacute stage, sometimes already after one to two weeks, the lesion will become less echogenic, with central echolucency, while in the chronic stage, after several weeks, cerebellar atrophy is seen. Depending on the size of the hemorrhage, the lesion may be focal or diffuse. In preterm infants with CBH, cerebellar atrophy is often seen around term equivalent age. However in cases of prenatal CBH, cerebellar atrophy may already be present at birth [34,35]. (See 'Prenatal presentation' above.)

CBH can occur in combination with extracerebellar, subdural hemorrhage. In the acute stage, these extracerebellar collections are often more echolucent than the parenchyma. Depending on their size, they may cause a mass effect on the cerebellum (image 13) [19].

Magnetic resonance imaging (MRI) — Although MRI provides images of areas that are difficult to visualize with ultrasound, MRI is not the initial preferred imaging modality in sick newborn infants, as it requires transportation to the magnetic resonance scanner. Thus, it is not a practical modality for early (shortly after birth) and serial neuroimaging for neonates at risk for cranial bleeding.

However, MRI does provide additional prognostic information in complicated cases, in whom defining location and extent of abnormalities is clinically necessary. In selected patients with (suspected) grade 2 to 3 CBH, we perform MRI at term equivalent age (when the infant is typically more clinically stable) to obtain information on chronic changes and on the effect of the lesion(s) on cerebellar growth and development. MRI also enables the detection and depiction of smaller, punctate lesions in the cerebellum and can provide more information about the extent of associated supratentorial injury and global brain development and maturation. Small, punctate lesions (<4 mm) are the most common type of CBH in preterm infants, and often are not detected by cranial ultrasound, despite the use of mastoid fontanel views [5-8]. Although MRI is a more sensitive modality, their presence on conventional magnetic resonance images can also be underestimated and influenced by factors such as magnetic resonance field strength and slice thickness. T2*-weighted and susceptibility-weighted sequences improve the detection of these small lesions, as these sequences are more sensitive to blood products and also show small hemosiderin depositions in tissue as areas with a hypointense signal (image 2 and image 4) [53].

Larger CBH are easily diagnosed on conventional MRI. In the acute stage and early subacute stage, these have high signal intensity on T1-weighted and low signal intensity on T2-weighted sequences. In the chronic stage, the hemorrhages often lead to destruction of cerebellar tissue and atrophy and can sometimes be mistaken for congenital cerebellar hypoplasia. The use of susceptibility-weighted or T2-weighted sequences also improves the recognition of hemosiderin in these chronic cerebellar lesions (image 1) [54].

Computed tomography (CT) — Although cerebellar abnormalities can be visualized by CT, it has no additional diagnostic value as compared with ultrasound and MRI [55]. It requires transportation to the scanner and also exposes the child to ionizing radiation. CT should therefore only be used in potential neurosurgical emergencies, such as cases with suspected acute symptomatic posterior fossa hemorrhage, where cranial ultrasound is inconclusive and MRI is not readily available.

DIAGNOSIS — Neonatal CBH is diagnosed by neuroimaging. Ultrasonography is the preferred technique as it can be performed at the bedside with little disturbance to the infant and does not involve ionizing radiation [8]. However, MRI is a more sensitive modality and can detect small punctate lesions that are often not detected by ultrasound. (See 'Neuroimaging' above.)

PREVENTION — The most effective strategy to prevent CBH is the prevention of preterm birth; however, this is yet to be accomplished. In the meantime, because it is likely CBH and supratentorial germinal matrix and intraventricular hemorrhage (GMH-IVH) share similar pathogenic mechanisms, both antenatal and early postnatal preventive measures used to reduce the risk of GMH-IVH are probably also effective in preventing CBH in preterm infants. (See "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in the newborn: Management and outcome", section on 'Prevention'.)

Our approach — We use the following approach to reduce the risk of CBH in very preterm infants (gestational age [GA] <32 weeks) based on indirect evidence of effective measures used in GMH-IVH and limited direct data on measures that reduce the risk of CBH. (See 'Risk factors' above and "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in the newborn: Management and outcome", section on 'Prevention'.)

Maternal, intrauterine transport in cases at risk for preterm delivery with gestation <32 weeks to a tertiary perinatal center with a neonatal intensive care unit (NICU). Transport of mothers at risk for preterm delivery reduces the risk of GMH-IVH and may thus also reduce the risk of CBH [56]. As very preterm infants (GA <32 weeks) born outside a level III neonatal intensive care unit (NICU) in general have a poorer outcome compared with inborn infants, maternal transport should be considered for mothers <32 weeks gestation to a facility with a level III NICU. (See "Inter-facility maternal transport" and "Preterm birth: Definitions of prematurity, epidemiology, and risk factors for infant mortality", section on 'Standard of neonatal care'.)

Antenatal administration of corticosteroids to pregnant women at 23 to 34 weeks gestation and at increased risk of preterm delivery within the next seven days. Antenatal corticosteroids given to mothers at risk for preterm delivery reduce the risk of neonatal respiratory disease and GMH-IVH (see "Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery"). Some studies also suggested a protective effect of antenatal corticosteroids on the development of CBH [10,25], but a subsequent meta-analysis [29] of the limited published data did not demonstrate a significant protective effect. Further research is needed to determine the efficacy of antenatal corticosteroids in reducing the risk of CBH.

Antenatal administration of magnesium sulphate to pregnant women at increased risk of preterm delivery between 24 and 32 weeks gestation. The use of antenatal magnesium sulphate was associated with a reduction in MRI-detected CBH [23] and the risk of cerebral palsy in preterm infants [31]. The exact mechanism is unclear, but stabilization of blood pressure and cerebral blood flow may play an important role. (See "Neuroprotective effects of in utero exposure to magnesium sulfate".)

Avoidance of breech or forceps extraction delivery Anticipation in cases with difficult presentation to avoid complicated breech or forceps extraction in preterm infants. Complicated breech extraction and forceps extraction may contribute to the development of CBH, in both term and preterm infants (image 13) [17]. In preterm infants who have a very compliant skull, external pressure on the occiput may result in altered venous drainage and elevation of venous pressure. In severe cases, it can also cause direct contusion of the cerebellar parenchyma. However, data from a meta-analysis showed that the mode of delivery (vaginal versus elective caesarean delivery) did not affect the risk of CBH [25,29]. (See "Overview of breech presentation".)

Prompt resuscitative efforts for nonvigorous preterm infants to avoid hypoxia and ischemia that may contribute to CBH. (See "Neonatal resuscitation in the delivery room".)

Respiratory support as needed to ensure adequate oxygenation and ventilation with avoidance of applying high pressure on the neonatal occiput during positive pressure ventilation and intubation. In particular, high mean airway pressures, hypocarbia, hypercarbia, acidosis, and abrupt PCO2 changes should be avoided in preterm infants with respiratory failure, who are at-risk for intracranial hemorrhage.

Careful management of blood pressure ‒ The management of low blood pressure (BP) in very preterm infants, especially extremely preterm infants (GA <28 weeks) remains challenging, as hypotension and fluctuations in BP should be avoided (see "Assessment and management of low blood pressure in extremely preterm infants"). Hypoperfusion may lead to ischemic events, while sudden increases in arterial blood flow due to volume resuscitation or the administration of inotropes may lead to rupture of vulnerable cerebral and cerebellar vessels. Careful, gradual fluid resuscitation and inotropic support are reserved for infants with low blood pressure with signs of inadequate perfusion (ie, neonatal shock). (See "Neonatal shock: Etiology, clinical manifestations, and evaluation" and "Neonatal shock: Management".)

Careful and minimal handling of very preterm infants – Minimizing handling of infants and painful procedures as much as possible without impacting clinical care also will reduce sudden rises in BP [57]. Avoid applying too much pressure on the occiput.

Unproven preventive measures

Thrombocyte transfusions There are insufficient data to determine if coagulation abnormalities contribute to an increased risk of CBH. Moreover, it is unclear whether correction of coagulopathy and thrombocytopenia reduces the risk of CBH. The optimal platelet threshold for prophylactic platelet transfusion remains unknown and as a result, the indications for platelet transfusion vary on the clinical setting and center [58]. In our practice, a threshold for prophylactic platelet transfusion of 25,000 per cubic mm is used for ill preterm infants, and only for cases with overt hemorrhage, a threshold of 50,000 per cubic millimeter is used.

In a randomized trial of preterm infants with severe thrombocytopenia, the rate of death and major bleeding was greater with a higher transfusion threshold than with a lower threshold [59]. These and other data are discussed elsewhere. (See "Neonatal thrombocytopenia: Clinical manifestations, evaluation, and management", section on 'Platelet transfusion'.)

Tocolytic therapy ‒ There are no data on the effect of tocolytic therapy on the risk of preterm CBH, but as it may delay or even prevent preterm birth, this may reduce the risk of CBH.

Treatment of chorioamnionitis ‒ The detection and treatment of chorioamnionitis has been associated with a decrease in the risk of GMH-IVH. A few studies have reported on the effect of chorioamnionitis on the risk of CBH. However, the definition varied or was not specified, and in a meta-analysis, no effect of chorioamnionitis on the risk of developing CBH was seen [29].

Treatment of patent ductus arteriosus (PDA) ‒ A meta-analysis reported an increased risk of CBH for preterm infants with a PDA (odds ratio 2.28, 95% CI 1.68-3.67) [29]. However, there is considerable controversy on the optimal management of PDA in preterm infants (conservative [watchful waiting], medical [pharmacologic therapy], and surgical treatment) as the choice of therapy does not appear to change outcome (mortality and major morbidity). Therefore, it remains unclear whether treatment may influence the risk of CBH. (See "Patent ductus arteriosus (PDA) in preterm infants: Management and outcome".)

MANAGEMENT — No specific therapy exists to limit the extent of CBH after it has occurred. Treatment of CBH is supportive and directed towards minimization of any further brain injury, and early detection of complications [60].

General measures include the following:

Maintenance of arterial perfusion to avoid hypotension or hypertension and sudden blood pressure changes, and to preserve cerebral blood flow without significant perturbations.

Adequate oxygenation and ventilation with specific avoidance of hypocarbia, hypercarbia, acidosis, and high mean airway pressures.

Provision of appropriate fluid, metabolic, and nutritional support.

In cases with active bleeding and thrombocytopenia, we transfuse platelets at a threshold of 50,000 platelets per cubic mm.

Serial cranial ultrasound examinations are performed to detect post-hemorrhagic ventricular dilatation (PHVD), which is a complication of both CBH and germinal matrix and intraventricular hemorrhage (GMH-IVH), especially within the first 2 weeks after the hemorrhage (see "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in the newborn: Risk factors, clinical features, screening, and diagnosis", section on 'Posthemorrhagic ventricular dilatation (PHVD)'). Further follow-up neuroimaging is performed to monitor cerebellar growth.

Long-term follow up with neurodevelopment assessment and access to early intervention programs. (See "Long-term neurodevelopmental impairment in infants born preterm: Risk assessment, follow-up care, and early intervention", section on 'Identifying at-risk infants' and "Long-term neurodevelopmental impairment in infants born preterm: Risk assessment, follow-up care, and early intervention", section on 'Early intervention programs'.)

OUTCOME

Mortality — Infants most likely to develop extensive cerebellar lesions are the sickest and most preterm; the majority of infants with such lesions have an unfavorable outcome. Older case series and autopsy studies indicated that infants with massive hemorrhages have high mortality rates [26,27,61]. However, with increased recognition of CBH, more patients survive and may have a more favorable outcome [4,62,63]. Functional outcome in these infants is related to the size and location of the hemorrhage and to concomitant supratentorial injury, as discussed below [62].

Neurodevelopmental outcome — There is increasing recognition on the long-term negative impact of neonatal CBH on neurodevelopmental outcome. A review of studies published between 2007 and 2014 describing neurodevelopmental outcomes of direct cerebellar injury in preterm infants confirmed that with the exception of punctate cerebellar lesions detected by magnetic resonance imaging (MRI), cerebellar injury is associated with long-term motor, cognitive, and language impairments, as well as socialization and behavioral difficulties [64]. Impaired outcome in infants with neonatal cerebellar injury depends on the site and extension of the lesion(s), the total volume of the lesions, whether there is concomitant supra-tentorial injury, and (based on limited data), further underdevelopment of the cerebellum and other regions of the brain [4,62,65].

For infants with large lesions detected by ultrasound, there is evidence of long-term neurodevelopmental impairment [4,24,62,65-68].

The impact of isolated CBH was demonstrated by a study that compared three groups of preterm infants (35 isolated CBH, 35 age-matched controls without CBH, and 16 CBH plus supratentorial parenchymal injury) [66]. Children with isolated CBH detected by ultrasound and confirmed by MRI were more likely than controls to have neurologic impairment (66 versus 5 percent) with lower scores on tests for motor, expressive and receptive language, and cognitive function. They also had more internalizing behavioral problems and more often an abnormal autism screening. These problems were most common and profound in cases with vermian involvement. The third group of preterm infants with combined CBH and supratentorial injury was not at overall greater risk for neurodevelopmental disabilities than those with isolated CBH, but their impairments were more severe.

A second study described the effects of CBH on outcome at preschool age of 79 survivors who were extremely preterm (gestational age [GA] <28 weeks) and had ultrasound detected CBH [24]. In this cohort, the location of hemorrhage was a predictor of the type of impairment; infants with hemorrhages involving both the medial and lateral structures of the cerebellum were at high risk for motor and mental disabilities, whereas infants with hemorrhages confined to only the cerebellar hemispheres had high rates of mental but not motor delay.

The outcome of punctate cerebellar lesions, frequently encountered as a chance finding on MRI, appears to be more favorable.

In a cohort of very preterm infants (GA <32 weeks) who underwent MRI at term age, small CBH were present in 15 percent of the infants. These small hemorrhages did not lead to disruption of cerebellar development or atrophy and were not associated with neuromotor outcome, or cognitive or behavioral problems at two years corrected age [5].

Another study also showed that the outcome of these small hemorrhages was more favorable than in infants with large CBH, but in this study, the infants still had a five-fold increased risk of neurologic abnormalities at five years compared with infants without CBH [6].

Evaluating the relationship between preterm CBH and outcome remains challenging, as published studies include small numbers of cases, and because affected infants, especially the most immature and sickest infants, usually have concomitant supratentorial injury. This makes it difficult to determine the impact of cerebellar injury alone and distinguish it from the effect of supratentorial hemorrhage and white matter injury. In addition, although the size and location of the lesion appear to impact outcome, only a few studies discriminate between sizes of lesions, and except for the presence of vermian involvement, there is little knowledge on the relationship between the location of cerebellar injury and outcome.

To address these issues, a 2017 systematic review of the literature analyzed the outcome of 128 very preterm infants with isolated CBH [69]. In this study, the incidence of severe delay in cognition, motor, language, and behavior development was 38 percent, 39 percent, 41 percent, and 38 percent, respectively. Infants with involvement of the vermis and those with large lesions had the highest risk of impaired outcome. A relatively low incidence of severe outcome was seen in patients with bilateral lesions, but this was likely due to the small number of patients (n = 6) with bilateral CBH. Infants with punctate cerebellar lesions had a much better outcome than infants with large cerebellar lesions. However, due to small subgroups and the lack of more detailed description, it was not possible to further evaluate the effects of size, laterality, and location on outcome.

In a subsequent retrospective multicenter study, the CHOPin study, 218 very preterm infants with CBH were classified by severity based on size (grade 1 punctate ≤4 mm, grade 2 limited >4 mm but <1/3 of a hemisphere and grade 3 massive ≥1/3 of a hemisphere) (table 1 and image 2 and image 3 and image 5 and image 6) (see 'Severity and grading' above) [4]. The following observations were made:

Outcomes at two years corrected age were similar between infants with punctate and limited lesions (grades 1 and 2), whereas infants with massive lesions (grade 3) had a significantly higher risk of impairments.

Subgroup analysis of infants without severe supratentorial injury (n = 87) found that the percentage of infants with abnormal outcome increased with increasing size of the CBH.

All infants with massive CBH and vermis involvement had an abnormal outcome.

Except for the punctate lesions, infants with bilateral lesions performed poorer, although the number of infants with bilateral grade 2 to 3 involvement was small (n = 10).

Subgroup outcome analyses based on location were not performed, as the number of infants based on specific locations was too small and precluded further analyses to determine a relation between locations of lesions and outcome. Nevertheless, the results from this study confirmed the importance of distinguishing between limited (grade 2) and extensive (grade 3) bleeds as those with limited CBH have better long-term outcome.

Volumetric MRI studies in preterm infants demonstrated that isolated CBH has a remote effect on the development of cortical areas functionally connected to the affected cerebellar region. In these infants, the volumes of remote cortical regions in the contralateral cerebral hemisphere were reduced as compared with those of the ipsilateral hemisphere [70]. The underdevelopment of cerebellar projection pathways and volumetric reductions of regional cerebral cortical areas of the contralateral cerebral hemisphere were predictive of domain-specific and long-term functional deficits [70]. This phenomenon is called cerebello-cerebral diaschisis.

In one study in which volumetric MRI was performed during the preterm period, both total size and location of CBH were associated with neurodevelopmental outcome at age 5.5 years [11]. Hemorrhages in the inferior posterior area and deeper regions of the cerebellum were associated with more motor, visuomotor and behavioral dysfunction than hemorrhages in the more superficial areas of the cerebellum.

Large, prospective multicenter studies may clarify possible associations between lesion size and location, and outcome. In addition, most of the above-mentioned outcome studies only included preschool outcome, and long-term follow-up is needed to determine the neurodevelopmental impact of CBH through school age, adolescence, and adulthood. These data will be imperative to identify the need for additional support for these individuals.

SUMMARY AND RECOMMENDATIONS

Epidemiology and risk factors – Cerebellar hemorrhage (CBH) is the major and most frequent cause of neonatal cerebellar injury in very preterm infants (gestational age <32 weeks). The risk of CBH increases with decreasing gestational age. In late preterm and term infants, CBH is associated with birth trauma, perinatal asphyxia, and major surgery. (See 'Epidemiology' above.)

Pathogenesis – The pathogenesis of CBH is similar to that of supratentorial germinal matrix/intraventricular hemorrhage (GMH-IVH) with bleeding occurring in a fragile highly vascular region of the brain during acute fluctuations of cerebral blood flow. Very preterm infants, especially extremely preterm infants (gestational age <28 weeks) are also more likely to be severely ill with concomitant conditions (eg, systemic hypotension, respiratory failure requiring mechanical ventilation and perinatal asphyxia) that result in additional hemodynamic disturbances that increase the risk of CBH. (See 'Pathogenesis' above and 'Risk factors for preterm infants' above and "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in the newborn: Risk factors, clinical features, screening, and diagnosis", section on 'Pathogenesis'.)

Fetal presentation – Fetal CBH, although infrequent, can be detected by fetal neuroimaging (image 9). At birth, infants with antenatally acquired CBH may present with either uni- or bilateral cerebellar hypoplasia which may mimic cerebellar malformation due to disruption of cerebellar development from the initial injury. (See 'Prenatal presentation' above.)

Preterm infant presentation – In preterm infants, CBH lesions can range from small punctate lesions detected by magnetic resonance imaging (MRI) to focal unilateral bleeds to massive bleeds involving both hemispheres including the vermis (table 1). Most CBH develop during the first postnatal week and are detected by screening cranial ultrasound examinations, including the mastoid fontanel approach. However, CBH may also develop later related to episodes of circulatory and/or respiratory failure. The smallest, punctate CBH are not well detected by screening cranial ultrasound examinations. (See 'Postnatal presentation of preterm infants' above.)

In preterm infants, most CBH are asymptomatic or present with nonspecific signs (eg, apnea, irritability, seizures, or ventricular dilatation unexplained by supratentorial abnormalities). Catastrophic presentation of CBH is rare and usually co-occurs with massive IVH. (See 'Postnatal presentation of preterm infants' above.)

Term infant presentation – Term infants with CBH generally present with early postnatal irritability, apnea or seizures. As these symptoms are nonspecific, cranial ultrasound should be performed to detect CBH (image 8). Some term infants will present with acute catastrophic deterioration, mainly when CBH occurs in combination with large extra-axial posterior fossa hemorrhage. (See 'Postnatal presentation of term infants' above.)

Diagnosis – The diagnosis of CBH is made by neuroimaging. Cranial ultrasound is the preferred imaging modality as it is performed at the bedside and enables early diagnosis. MRI performed around term equivalent age is used to determine exact location and extent of the lesion(s). It also helps to determine cerebellar disruption or atrophy due to antenatal or neonatal CBH and to detect punctate CBH. (See 'Neuroimaging' above and 'Diagnosis' above.)

In our centers, screening cranial ultrasound examinations are performed serially during the first postnatal week for very preterm infants. Mastoid fontanel windows are used to assess the posterior fossa during at least one of these routine ultrasound scans and on a regular basis for subsequent serial ultrasound examinations. (See 'Cranial ultrasound' above.)

Prevention – The most effective strategy to prevent CBH is to reduce the risk of preterm birth. When preterm birth cannot be avoided, appropriate prenatal and neonatal care should be provided to the mother and neonate including maternal, intrauterine transport, administration of antenatal corticosteroids and magnesium sulfate, avoidance of a complicated breech or forceps extraction delivery, prompt and appropriate neonatal resuscitation, and judicious management of ventilation and blood pressure. (See 'Our approach' above and "Inter-facility maternal transport" and "Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery" and "Neuroprotective effects of in utero exposure to magnesium sulfate" and "Overview of breech presentation" and "Neonatal resuscitation in the delivery room" and "Assessment and management of low blood pressure in extremely preterm infants" and "Neonatal shock: Etiology, clinical manifestations, and evaluation".)

Management – No specific therapy exists to limit the extent of CBH after it has occurred. Treatment of CBH is supportive and directed towards minimization of any further brain injury, and early detection using follow-up cranial ultrasounds of complications including post-hemorrhagic ventricular dilatation (PHVD). (See 'Management' above.)

Outcome – Outcome in infants with neonatal cerebellar injury depends on the site and extension of the lesion(s) and whether there is concomitant supra-tentorial injury. Extensive lesions are associated with poor outcome with high mortality rates and neurodevelopmental impairment in the majority of survivors. For surviving infants, long-term neurodevelopmental follow-up is therefore needed. (See 'Outcome' above.)

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References

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