Intracranial Hemorrage

Intracranial hemorrhage (ICH) refers to hemorrhage within the fetal cranium. ICH is a common occurrence in the premature infant. In the fetus the condition is rare and the pathophysiology probably different. Only a limited number of cases of the detection of fetal intracranial hemorrhag have been reported.^1-15

Germinal matrix hemorrhage, intraventricular hemorrhage, intraparenchymal hemorrhage, subdural hematoma.

Intracranial hemorrage occurs rarely in utero. The global incidence has been estimated in the range of 1:10,000 pregnancies, although this probably represent an underestiumation.

Factors predisposing to in utero ICH include a variety of conditions, most frequently maternal trauma and fetal coagulation disorders, including alloimmune thrombocytopenia and maternal use of anticoagulants crossing the placenta.^{1, 5, 9-11, 13, 14} The most common risk factor for intracranial hemorrhage seems to be platelet disorders. Immune thrombocytopenic purpura (ITP), in rare cases, can produce fetal thrombocytopenia severe enough to cause fetal hemorrage prior to labour.¹⁶ Although rare, alloimmune thrombocytopenia is an even more predictable inducer of fetal thrombocytopenia and has been linked to cases of fetal hemorrage prior to the onset of labor.It is estimated that in alloimmune thrombocytopenia, 20% of offspring can suffer intracranial hemorrhage, half of which may occur in utero.^17-20 Hidden maternal autoimmunity (that is the presence of antiplatelet antibodies in a patient with a normal platelet count) has also been reported as a predisposing condition to fetal hemorrage.²¹ In about 50% of cases, however, the cause of fetal ICH is not identified.⁵

There are different types of intracranial hemorrhages Probably the most common in the fetus, is intraventricular hemorrhage.1, 3, 5, 13 In premature infants this hemorrhage most commonly originates in the subependymal germinal matrix region. This contains thin-walled friable vessels supported by a delicate matrix that is easily injured. In the fetus the pathogenesis may be different, and it is possible that hemorrages derive at least in some cases from the choroid plexuses.

Only major fetal intracranial hemorrhages are probably recognized prenatally. Small hemorrhages may resolve and disappear completely. More significant hemorrages may lead to blood accumulation in the lateral ventricles, third ventricle and aqueduct of Sylvius. Debris may obstruct the acqueduct and result in hydrocephalus. In severe cases, hemorrhage may cause a destructive process of the periventricular white matter ultimately causing a porencephalic cyst.

Similarly to neonates, intraventricular hemorrage is commonly classified in 4 grades::

Grade I – limited to supendymal matrix;

Grade II – clear spill-over to ventricles, but filling less than 50% of the lateral ventricle and consequently without acute ventriculomegaly;

Grade III – spill-over to the ventricle, with acute dilatation because of flooding of 50% or more of one or both lateral ventricles;

Grade IV – grades 1,2 or 3 with destruction of a more or less large part of the periventricular parenchyma.

Other types of intracranial hemorrages that have described antenatally include subdural hematoma5, 8, 10, 15 and cerebellar hemorrhage5, 14.

Usually, there are no associated anomalies with in utero intracranial hemorrhage. Associated defects are secondary to underlying etiologies of thehemorrhage such as growth restriction, trauma or coagulopathy.

Haemorrage most frequently occurs within the lateral ventricles where the accumulation of blood appears initially as an echogenic collection without posterior shadowing, similar to the normal choroid plexus. In the following days blood clots develop a complex texture with an external echogenic lining and an internal sonolucent core (Figure 1). At this stage there is usually some degree of enlargement of the lateral ventricles, that demonstrate typically a brightly echogenic lining. With time, small intraventricular haemorrhages may undergo spontaneous resolution. On the other hand, large haemorrages usually result in obstruction to the cerebro-spinal fluid circulation at the level of the aqueduct of Sylvius, resulting in severe distension of the lateral and third ventricle. They can also be associated with infarction and destruction of the white matter surrounding the ventricle, which eventually results in a porencephalic cyst.. The diagnosis of fetal intraventricular/periventricular haemorrage is not always easy. In dubious cases, serial examinations will demonstrate a typical pattern of evolution..

Subdural hematomas are probably the most difficult entity to recognize precisely in utero, and differentiation from other intracranial masses, such as tumors, may be difficult.5, 10, 12 In our experience, a large subdural hematoma will typically appear as a complex mass compressing and distorting the hemispheres.5, 10

Cerebellar hemorrage is suggested by the demonstration of an echogenic collection into the posterior fossa, usually obscuring the cerebellum.4, 5, 14 Differentiation from a primary ischemic lesion of the cerebellum is difficult and frequently is not possible. Usually, both these disorders will lead in time to hypoplasia of one or both cerebellar hemispheres, sometimes mimicking a Dandy-walker malformation.

Magnetic resonance may be useful both to confirm the sonographic diagnosis of an intracranial hemorrage, as well to better assess the grade.2, 5, 11

With severe hemorrage and subdural hematomas the use of spectral Doppler has occasionally documented increased pulsatility of the middle cerebral artery with absent or reverse diastolic flow, probably as a consequence of acutely increased intracranial pressure.15

The differential diagnosis for intracranial hemorrhage would seem limited. Certainly if the intracranial hemorrhage is large or involves a brain substance and has a mass effect, this may be mistaken for intracerebral neoplasm. In dubious cases, fetal MRI may be performed and willl usually be diagnostic. Alternatively, serial sonograms could be performed. The apperance of an intraparenchymal hemorrage changes with time. At first a purely echogenic lesion is found. In 1-2 weeks, the blood clots tend to develop an hypoechogenic core, while ventricles will become enlarged and/or a porencephalic cyst will appear. The differential dianosi for ventriculomegaly caused by intraventricular hemorrhage would include other etiologies of ventriculomegaly. Etiologies for ventriculomegaly could include hydrocephalus from a number of causes; developmental abnormalities of the brain; or destructive abnormalities of the brain. The presence of irregular echogenic areas within the ventricles is indicative of an hemorrage.

The prognosis for fetal intracranial hemorrage has been documented to include mild neurological deficit such as mild esotrophia and hemiparesis to newborn death. In general, the outcome of cases described in the literature thus far has been disappointing. In a review of the literature perinatal death occurred in about 50% of cases and 50% of survivors had neurologic compromise at long term follow-up.5 There was a correlation between the outcome and the grade of the hemorrhage. The prognosis was more favorable with grade 1 and 2 hemorrhages, that at times may even resolve in utero, and was usually severe with grade 3 and 4 hemorrhages. Fetal subdural hematomas have an outcome similar to severe hemorrage.15 Cerebellar hemorrage may be more benign, although the available experience is limited.5, 22

It must be pointed out that probably thus far the capability of ultrasound instrumentation only allowed the detection of very severe intracranial hemorrage. It is likely that technological improvements and the widespread use of high resolution vaginal probes will allow in the future detection of less severe lesions, with a better outcome.

An attempt should always be made to identify the etiology of the intracranial hemorrhage. An interview should focus on obstetric history, drug use or recent trauma (motor vehicle accident, fall onto the abdomen, others). Diagnostic workup should always include laboratory test for the possible presence of a fetal platelet disorder.This should include maternal platelet count and testing for maternal both alloimmunity23, 24 and isommunity.25 In pregnancies complicated by immune thrombocytopenia (ITP), many therapies can be used to increase maternal platelet count including corticosteroids, intravenous immunoglobulin, vinca alkaloids, danazol, dapsone, etc but the efficacy of these treatment in preventing neonatal complications is unproven.26. Cesarean delivery was been originally proposed to decrease the risk of intrapartum hemorrage in thrombocytopenic fetuses of mothers with ITP. However, the recent evidence indicates that in these infants hemorragic complications occur indepedently from the mode of delivery. In one study, intracranial hemorrage occured in 4% of infants delivered vaginally and 3% of those delivered with a cesaream section.27 In fact, it remains unclear wether the hemorrage in these cases occurs intra-partum or in the imemdiate neonatal period. At present, the mode of delivery is independent of the presence of maternal ITP.25 Treatment of alloimmune fetal thrombocytopenia is still a matter of debate. The much higher incidence of fetal hemorrage in these cases certainly justifies a more aggressive management than with ITP. The therapeutic alternatives include maternal administration of intravenous immune globulin with or without steroids and fetal platelet transfusions. The interested reader is referred to specific work on this subject..17, 18, 20Whether treatment would be indicated in the face of an already established fetal intracranial lesions is uncertain.

In many cases, as there is no recognizable etiology for the intraventricular intracranial hemorrhage, there will be no potential for future prevention. However, other etiologies such as drug-induced intracranial hemorrhage can be prevented by stoppage of the drug use during future pregnancies. Prevention of problems in pregnancies complicated by alloimmune thrombocytopenia should be aimed at identification of the condition and proper counseling and management. Alloimmune thrombocytopenia should be suspected in all patients with a infant with unexplained thrombocytopenia, hemorrage or porencephaly. These couples should be addressed to a center with expertise dealing with the problem. Recently, it has been suggested that screening the entire obstetric population for this condition may be justified.²³

Please note that the maximum upload size is 5MB, and larger images and video clips can be sent to [email protected].