*   Department of Gynecology, Félix Guyon'Hospital, 97400 Saint-Denis, Ile de la Réunion, France, Tel : 0262 90 55 22. Fax : 0262 90 77 30
**  Gynecologist, Sainte-Clothilde clinic, 97400 Saint-Denis, Ile de la Réunion, France.
*** Department of Neonatology, Félix Guyon'Hospital, 97400 Saint-Denis, Ile de la Réunion, France.

Definition
Prenatal finding of intracranial hemorrhage has been widely reported. Hemorrhage can occur anywhere in the fetal cranium, but prenatally is mostly identified as an intraventricular hemorrhage. Bleeding can take place within subarachnoid, subdural, or intraparenchymal locations too. The most of prenatally diagnosed intracranial hemorrhages are located in the supratentorial area and less frequently in infra-tentorial fossa [1]. Germinal matrix-intraventricular hemorrhage in the fetus is very rare [2].

We report a case of prenatal ultrasound and MRI diagnosis of germinal matrix - intraventricular hemorrhage in a 32-week fetus. The newborn had posthemorrhagic ventriculomegaly, but his postnatal clinic examination was normal.

Case report
A 20-year-old primigravida with normal first and second trimester ultrasonographic and biochemical screening and with insignificant history. At 32nd week of pregnancy the ultrasound investigation revealed cerebral ventriculomegaly and intraventricular clots (an irregular, hyperechogenic mass), localized inside the lateral ventricles, near the posterior part of choroid plexus (see pictures 1, 2, 3, 4).
Ultrasound scans of the fetal head showed diffuse hyperechogenicity around the ventricles, with a hematoma near the posterior part of the ventricles (see pictures 5, 6, 7, 8, 9, 10, 11). 
Maternal-serum screening (Rubella, CMV, Herpes, Parvovirus B19, Coxsackie, Chikungunya, and Toxoplasmosis) and maternal coagulation parameters were normal. The Kleihauer-Betke test and antiplatelets antibodies were negative. 
A prenatal MRI scan, performed at 33rd week of pregnancy, confirmed the ventricular dilatation and the presence of intra-ventricular bleeding originating from the caudal thalamic notch (see pictures 12, 13, 14, 15). The appearance was consistent with the typical germinal-matrix intraventricular hemorrhage occurring in preterm newborns.
At 35-week of pregnancy ventriculomegaly increased (see picture 17).
The patient gave birth at 38th week of pregnancy. Clinical examination of the baby was normal, serologic and coagulation parameters were normal too. Postnatal MRI confirmed our diagnosis.

Pictures 1, 2, 3, 4 - echogenicity around lateral cerebral ventricles

Pictures 5, 6, 7, 8, 9, 10, 11 - parasagittal and coronal planes of the brain

Pictures 12, 13, 14, 15 - MRI scans of the brain at 33rd week of pregnancy

Picture 17 - parasagittal plane of lateral ventricles at 35th week of pregnancy

History
The sonographic diagnosis of fetal intracranial hemorrhage was first reported in 1982, in a patient with recurrent episodes of pancreatitis and a fetal demise at 29th week of pregnancy. The earliest prenatal diagnosis of intracranial hemorrhage was done at 20th week of pregnancy in a fetus with ventriculomegaly and a large temporooccipital mass [2].

Prevalence
Intracranial hemorrhage is a common event in premature infants. It is found in 21 % of preterm infants at autopsy, but this form of intracranial bleeding is rare in mature fetuses and only few cases have been described [3].
Some authors estimate that the actual prevalence of fetal intracranial hemorrhage is approximately 5 in 10.000 pregnancies [2, 4]. Only a few cases of isolated infratentorial hemorrhage, diagnosed in utero, have been described so far.

Etiology
The cause of fetal intracranial hemorrhage is not always clear and in many cases the cause of bleeding cannot be identified [5]. Intracranial hemorrhage has been reported in pregnancies with maternal or fetal complications like maternal abdominal trauma, pancreatitis, cholestasis, pre-eclampsia and epileptic seizures, drug abuse (cocaine), ingestion of platelets function altering medicaments, fetal coagulation disorders, asphyxia, intra-uterine infection, congenital vascular defects [6, 7, 8].
Fetal coagulations disorders include factor V or X deficiency, as well as impaired fetal coagulation from maternal warfarin therapy, alloimmune and isoimmune idiopathic thrombocytopenia, autoimmune thrombocytopenia have also been related to the fetal intracranial hemorrhage. Congenital tumors, twin-twin transfusion, demise of a co-twin or fetomaternal hemorrhage can be responsible for intracranial hemorrhage of the fetus either [9, 10].

Pathogenesis
In the fetus, much than in the newborn, the pathogenesis of germinal matrix intraventricular hemorrhage is likely to depend on individual predisposing factors such as hemodynamic disturbances (twin-twin transfusion, fetomaternal transfusion), hemorrhagic diseases, thrombocytopenia or congenital infection.
In most cases, intracranial bleedings, including intra-ventricular hemorrhage, are thought to occur during labor or in the first week of life. However, intracranial bleedings occasionally can occur before birth [1]. Sudden changes in the cerebral blood pressure may cause hemorrhage from fragile capillaries of the subependymal germinal matrix. Prenatal asphyxia can induce increasing of cerebral blood flow and pressure with subsequent capillary rupture. The immature vessels of the periventricular germinal matrix or subependymal vessels are especially vulnerable to such an insult. Thin wall between cerebral ventricles and germinal matrix may be ruptured during hemorrhage and blood gets into the ventricles — intraventricular hemorrhage. This can possibly lead to ventricular dilatation (obstruction of the aqueduct of Sylvius by blood clots).

Sonographic findings
Sonographic findings of fetal intracerebral hemorrhage are variable. In general, the condition is considered to be difficult to identify and to differentiate it from other intracranial lesions. A recent hemorrhage appears as a brightly echogenic collection without posterior shadowing. During following days, blood clots become visible as a complex echogenic texture with external echogenic lining and an internal sonolucent core. Intraventricular blood clots are usually associated with distension of the ventricles, which initially demonstrate a typical echogenic lining. Interventricular hemorrhage can lead obstruction of the cerebrospinal fluid circulation, usually at the level of the aqueduct of Sylvius resulting in ventriculomegaly. Involvement of the cortex can be predicted by demonstration or extension of the echogenic collection to the paraventricular parenchyma in the early stages, or by formation of porencephalic cysts, usually about two weeks after the hemorrhagic event. A bright area around the cerebellum may prompt the diagnosis of an infratentorial hemorrhage [4].

Implications for targeted examinations
Intraventricular hemorrhages were categorized by the classification, classically used in neonates as follows. Grading of paraventricular lesions was adapted from the method of Vries et al. [2] as follows:
Grade 1: Limited to subependymal matrix
- Grade 1A: Moderately increased echogenicity, the periventricular white matter being as bright or almost as bright as the choroid plexus.
- Grade 1B: Seriously increased echogenicity, the periventricular lesion white matter being brighter than the choroid plexus.
Grade 2: Transient periventricular densities turning into small, frontoparietally localized cysts. Hemorrhage spills-over to the ventricle, but fills less than 50% of the lateral ventricle and without ventriculomegaly.
Grade 3: Periventricular densities evolve into extensive periventricular cystic lesions. The hemorrhage spills-over the ventricle, with flooding of 50 % or more percent of one or both lateral ventricles with ventriculomegaly.
Grade 4: Densities extend into deep white matter and create extensive cystic lesions.
Gui et all proposed to classify intraventricular hemorrhage in accordance with a transverse diameter of the lateral ventricular atrium of < 15mm as grade II, and those cases with a diameter > 15mm as grade III.

Prognosis
Management of intra-cranial hemorrhage in the fetus is very problematic. Intracranial bleedings visible by transabdominal sonography are usually extensive. Intracranial hemorrhage in utero has been reported to be cause of hydrocephaly, non immune hydrops with severe fetal anemia. Indeed, survivors face the same potential complications as the neonate with intracranial hemorrhage, including the potential for development of hydrocephaly and neurodevelopmental delay. Unfortunately, in utero, sonographic evaluation alone may miss significant associated pathology, such as porencephalic cysts and subarachnoid hemorrhage. These findings may have influence on prediction for neonatal outcome.
Results of Gui et all and the review of the literature suggest that prenatally diagnosed intracranial hemorrhages have a poor outcome. About 40 % of fetuses die either in utero or within the first month of life. Among the survivors, less than half appear neuro-developmentally normal at short term follow-up [4].
The survival rate is similar from subdural hematomas and intraventricular hemorrhage, but at a follow up of one year, a slightly better outcome was observed with subdural hematomas than with intraventricular hemorrhage (normal development in 67 % versus 48 %) [4]. In accordance with postnatal studies the outcome of fetal intraventricular hemorrhage was strongly related to the grade of the lesion. Perinatal mortality with grades 1 and 2I was 7 %. Perinatal mortality with grades I3 and 4 was 44% [4].

References

1. Catanzarite V.A., Schrimmer D.B., Maida c., Mendoza A. Prenatal diagnosis of intracranial haemorrahge : report of a case with a sinusoidal fetal heart rate racing and review of the literature. Prenat Diagn 1995 ; 15 : 229-335.
2. De Vries L.S.- Improved antenatal detection of hemorrhagic/detection intracranial lesions using transvaginal ultrasonography and fetal magnetic imaging. Ultrasound Obstet Gynecol 2003 ; 22 : 108-9.
3. Yüksel A ;, Batukan C.- fetal cerebellar hemorrhage in aseverely growth-restrcited fetus : natural history and differential diagnosis from dandy-Walker malformation. Ultrasound Obstet Gynecol 2003 ; 22 : 178-81.
4. Gui T., Simonazzi G., Perolo A., Savelli L., Sandri F., Bernardi B., Santini D., Bovicelli L., Pilu G.- Outcome of antenatally diagnosed intracranal hemorrahge case series and review of the literrature. Ultrasound Obstet Gynecol 2003 ; 22 : 121-30.
5. Gorincour G., Rypens F., Lapierre C., Costa T., Audibert F., Robitailles Y.- Fetal magnetic resonance imaging in the prenatal dagnosis of cerbellar hemorrhage. Ultrasound Obstet Gynecol 2006 ; 27 : 78-80.
6. Moinuddin A., McKinstry R., Martin A.K., Neil J.J.- Intracranial hemorrhage progressing to porencephaly as a result of congenitally acquired cytomegalovirus infection-an illustrative case. Prenatal Diagnosi 2003 : 797 ;800.
7. Ramengui L.A., Fumagalli M., Righini A., Triulzi F., Kustermann A., MoscaF.- Thrombophilia and fetal germinal matrix-intra-ventricular hemorrhage : does it matter ? Ultrasound Obstet Gynecol 2005 ; 26 : 574-6.
8. V an Gelder-Hasker M.R., Van Wezel-Meijler G., De Groot L., Van Geijn H.P., De Vries J.I.P.- Peri- and intraventricular cerebral sonography in second- and third-trimester high-risk fetuses : a comparaison with neonatal ultrasound and relation to neurological development. Ultrasound Obstet Gynecol 2003 ; 22 : 110-20.
9. Whitelaw A., Haines M.E., Bolsover W., Harris E.- Factor V deficiency and antenal intraventricular haemorrahge. Arch Dis Child 1984 ; 59 : 997-9
10. Zanders E.H.J., Buist F.C.D., Van Vugt J.M.G.- Prenatal dignosis of fetal intracranial hemorrhage at 25 WG. Fetal Diagn Ther 2003 ; 18 : 32 : 4-7.