Ventriculomegaly (VM) is a commonly detected prenatal ultrasound finding that can indicate various pathologic processes or be a normal variation. Depending on its etiology, severity, and progression, VM can lead to a range of neurodevelopmental outcomes, from normal to delayed, as indicated in sources [2, 4, 12, 19, 20]. In this study, we provided a comprehensive analysis of the etiologies and prognostic factors associated with VM, and identified that non-isolated VM cases exhibited a higher incidence of bilateral, severe, and progressive characteristics compared to isolated VM cases. The fetal VM prognosis is impacted by the degree of ventricle dilatation, progression, and any accompanying structural anomalies, with particular consideration for CNS anomalies and multiple anomalies (fetal VM with both CNS and non-CNS anomalies).
Ventriculomegaly refers to the enlargement of ventricles that is not caused by an obstructive cause, unlike hydrocephalus that is caused by increased cerebrospinal fluid (CSF) pressure as a result of obstruction[2]. VM can be associated with genetic, structural, and fetal TORCH infectious disorders, with outcomes varying from normal to severely impaired. In VM fetuses, around 5% of cases of mild to moderate VM cases were reported to be caused by congenital infections, and 5% had an abnormal karyotype. Additionally, 10–15% showed abnormal findings in chromosomal microarray analysis (CMA)[2]. CNS anomalies were observed in 50–85% cases of severe VM[6]. This study demonstrated that non-isolated VM cases had a higher prevalence of bilateral (52% vs. 25%), severe (12% vs. 2%), and progressive (16% vs. 10%) characteristics when compared with isolated VM.
It is widely accepted that infants VM, who have accompanying CNS anomalies, or those who have severe or progressive VM, have worse outcomes compared to those with mild isolated VM or VM that resolved spontaneously[11, 19, 20]. When VM accompany CNS or non-CNS malformations, the likelihood of neurodevelopmental delay increases from 9–36% in isolated cases to 84%[6, 21, 22]. Our data, in line with most studies[1, 4–6, 9, 10, 23], demonstrates that fetuses with neurodevelopmental delay often have structural anomalies in the central nervous system, urogenital system, heart, gastrointestinal tract, and spine. Multiple anomalies and CNS structural anomalies, such as mega cisterna magna and agenesis of corpus callosum, were found to be associated with a higher risk of developmental delay. Early studies have generally considered mega cisterna magna as a harmless abnormality[24, 25]. However, Dror et al.[26] reported that children with an enlarged cisterna magna might be at risk of mild developmental delay, particularly for non-isolated cases, after conducting the Gesell Developmental Schedules and the Peabody Developmental Motor Scale tests on 29 children with a large cisterna magna found in utero and 35 normal controls. Furthermore, respectively, urogenital system and gastrointestinal tract anomalies were associated with higher odds of low MDI and PDI scores.
According to recent research on genetic testing of karyotype and chromosomal microarray (CMA), invasive examinations should be considered for all women with VM in utero, irrespective of age, due to the higher rate of genetic aberrations, additional anomalies, and poor prognoses[5, 27]. As mentioned previously, we have observed a lower incidence of abnormal karyotype and CMA results compared to prior studies. Our study observed that infants with or without genetic variants categorised as “variants of uncertain significance” had similar outcomes on measures of BSID-CR during short-term follow-up. Although our sample is insufficient to draw a final conclusion, our data suggest that, unlike chromosomal abnormalities, the unclear pathogenic genetic disorder of ventriculomegaly fetuses does not predict the risk of poor outcomes.
It has been reported that progressive and severe lateral ventricular dilatation was correlated with worse neurodevelopmental outcomes, but the reported impact on different aspects of neurologic functions is inconsistent[3, 20, 28]. Regarding progression, multiple reviews and studies have reported that intrauterine progression of VM is only associated with motor impairment[11, 28]. Our findings are consistent this concept. As for the severity of VM, severe VM (atrial width above 15mm) is considered the primary factor that affects pregnancy outcomes and it is generally associated with a poor neurodevelopmental outcome[5, 20, 23]. Our study also confirms this. However, some literature suggests that the severity of VM is not consistently or directly associated with outcomes[10, 20, 28]. Additional population-based studies with objective protocols for prenatal diagnosis and postnatal neurodevelopmental evaluation are required to clarify these issues.
Our study has certain limitations. The first limitation is the early endpoint of the neurodevelopmental follow-up. A comprehensive evaluation requires considering the progressive trajectories and extended follow-up of the neurodevelopmental outcomes. Secondly, some parents perceived their children as relatively normal and, as a result, did not participate in further postnatal follow-up. Lastly, due to the absence of an evaluation of the caregiving quality of the family environment, the study has another limitation. Early intervention may have a more significant effect on maximizing the developmental potential of infants with developmental issues[29], making this assessment crucial.