Deep dive into fetal ventriculomegaly

Ventriculomegaly is a term used to describe the dilation of the cerebral ventricles within the fetal brain. Ventriculomegaly can be caused by several different disorders, including structural brain malformations, genetic abnormalities, congenital infections, and teratogens.

Fetal ventriculomegaly is a relatively common finding on second-trimester obstetric ultrasound examination. The prevalence of ventriculomegaly is approximately 0.15% in the general obstetric population.¹

Diagnosis of ventriculomegaly is usually initially made on ultrasound with routine prenatal screening. It is then further classified based on the severity of the enlargement. The diameter of the ventricles remains stable throughout pregnancy, with the upper limit of normal being less than 10 mm.^1-6 Mild ventriculomegaly is a ventricular diameter between 10 and 12 mm. Moderate ventriculomegaly is a ventricular diameter of 13 to 15 mm. Severe ventriculomegaly, or hydrocephalus, is a ventricular diameter of greater than 15 mm (Figures 1 and 2).⁷

Another common ultrasound finding with ventriculomegaly is where the choroid plexus appears to fall toward or rest on the dependent wall of the lateral ventricle, resulting in an increased angle, or “dangling,” of the choroid plexus (Figure 3).⁸ Approximately half the cases of ventriculomegaly are unilateral, and the other half are bilateral.^7,9,10 The causes and perinatal outcomes of unilateral and bilateral ventriculomegaly are similar, thus their management is the same.¹¹

Isolated mild ventriculomegaly is usually a normal variant and is associated with normal neurological outcomes. Isolated moderate ventriculomegaly has also been associated with normal outcomes, although less likely as compared with mild.⁷ Pathologic ventriculomegaly can either be due to excessive cerebrospinal fluid (CSF) production, obstruction, or loss of cerebral tissue. As stated above, these pathologic causes include idiopathic or genetic and chromosomal disorders (commonly trisomy 21, 18, and 13).

Other genetic syndromes are also associated with ventriculomegaly, such as X-linked hydrocephalus and other microdeletions/microduplications. Congenital infections such as cytomegalovirus, toxoplasmosis, rubella, or Zika virus can cause ventriculomegaly by cerebral atrophy, or obstruction from fibrosis and inflammation. Structural malformations such as aqueductal stenosis, agenesis of the corpus callosum, and neural tube defects have all been associated with ventriculomegaly. Other causes include obstruction from mass effect, intracranial hemorrhage from vascular abnormalities, teratogens, and, although rare, excessive CSF production by a choroid plexus tumor.

The management of fetal ventriculomegaly depends on the underlying etiology and severity of the condition and typically requires a multidisciplinary approach involving obstetricians, maternal-fetal medicine specialists, pediatric neurologists, and genetic counselors. Therefore, the necessary recommended steps after initial diagnosis include a detailed anatomic survey to assess for any other central nervous system malformations, any other associated structural fetal malformations that are typically found with genetic syndromes or fetal infections,^12-16 fetal biometry, as ventriculomegaly can be linked fetal growth restriction—especially if associated with a genetic abnormality,⁷ genetic counseling to offer diagnostic genetic testing for chromosomal microarray, infectious polymerase chain reaction, alpha-fetoprotein, and acetylcholinesterase if there is suspicion for a neural tube defect,^17,18 and testing for single gene disorders or consideration for exome sequencing if initial genetic testing is normal.

MRI should be considered in cases of ventriculomegaly, especially in cases with no clear etiology or where ultrasound is not conclusive in ruling out other malformations. A meta-analysis that assessed the increased diagnostic yield of MRI based on the type of ultrasound assessment showed that MRI detected additional anomalies in 5% to 16% of fetuses with mild or moderate ventriculomegaly. These additional findings are vital for parental counseling and can change perinatal management in 3% to 5%.¹⁹ Given that neurological malformations can be associated with a wide range of pediatric outcomes from normal to severe neurological delays, prenatal counseling is often difficult, as it leaves many parental questions unanswered until after the fetus is born. Because of this, in situations such as isolated mild ventriculomegaly, confirmation of this through MRI can provide some relief to parents as the majority have normal long-term neurological outcomes. In addition, certain neurological findings, such as cortical or sulcation malformations, and migrational abnormalities may not be easily diagnosed on prenatal ultrasound but can be detected by MRI.^20-22

Again, the prognosis is also dependent on the etiology and severity of ventriculomegaly. For example, if the etiology has been confirmed due to aneuploidy, then the parents should be informed that the prognosis is typically dependent on that specific aneuploidy. However, etiology cannot always be confirmed prenatally, and parents should be informed of the wide variation of outcomes. Neurological, motor, and cognitive delays are more likely with severe ventriculomegaly, with meta-analysis reporting rates as high as 58% as compared with greater than 90% in cases of isolated mild to moderate ventriculomegaly.^13-15,17,23 The prognosis is also worse if there is the presence of other structural malformations or a progression of the ventriculomegaly as gestation advances.^13,24,25

Sonographic follow-up and serial monitoring are recommended to evaluate progression or persistence. Isolated mild ventriculomegaly can also resolve throughout the pregnancy.²⁶In a study involving 106 liveborn infants, ventriculomegaly showed varying trends during fetal development. Among these infants, 19 (18%) experienced an increase in ventriculomegaly before birth, whereas 37 (35%) remained stable and 50 (47%) either improved or resolved before birth.²⁶ Of the cases where ventriculomegaly improved, 92% (46 of 50) had normal outcomes. This contrasts with outcomes in cases where ventriculomegaly remained stable (35%; 13 of 37) or worsened (21%; 4 of 19). Overall, the progression of ventriculomegaly before birth was linked to adverse outcomes in 44% of cases vs only 7% in cases where ventriculomegaly did not progress.

Consultation with a pediatric neurosurgeon may be advisable if ventriculomegaly shows signs of progression. Although rare, some newborns may require surgical procedures such as ventriculoperitoneal shunting; however, this intervention is still considered investigational.

Antepartum fetal testing, such as nonstress tests or biophysical profiles, has not been shown to provide clear benefits in pregnancies where fetal ventriculomegaly is isolated and there are no other fetal conditions (eg, growth restriction or low amniotic fluid levels) or pregnancy complications that are known to increase the risk of fetal loss.

The timing of delivery is typically based on usual obstetrical indications, as there is a lack of high-quality evidence that shows improved perinatal outcomes with earlier delivery, and there are known adverse neonatal outcomes with preterm delivery. Some authors have suggested earlier delivery in cases of progressive severe ventriculomegaly to expedite postnatal shunting.²⁷ The mode of delivery is also typically based on usual obstetrical indications, as there is a paucity of data to show improved perinatal outcomes with cesarean section. For fetuses with macrocephaly, typically with head circumferences exceeding 40 cm, some authors suggest planned cesarean section.²⁸

In conclusion, fetal ventriculomegaly is a multifaceted condition demanding thorough assessment and treatment to enhance outcomes for both the fetus and the family. Progress in prenatal imaging and genetic testing has enhanced our capacity to diagnose and define ventriculomegaly before birth, facilitating prompt intervention and well-informed decision-making. Ongoing research is essential to deepen our understanding of the root causes of ventriculomegaly and to devise more efficient treatments for those affected.

References

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