Prenatal mild ventriculomegaly predicts abnormal development of the neonatal brain

Abstract

Background: Many psychiatric and neurodevelopmental disorders are associated with mild enlargement of the lateral ventricles thought to have origins in prenatal brain development. Little is known about development of the lateral ventricles and the relationship of prenatal lateral ventricle enlargement with postnatal brain development.

Methods: We performed neonatal magnetic resonance imaging on 34 children with isolated mild ventriculomegaly (MVM; width of the atrium of the lateral ventricle >/= 1.0 cm) on prenatal ultrasound and 34 age- and sex-matched control subjects with normal prenatal ventricle size. Lateral ventricle and cortical gray and white matter volumes were assessed. Fractional anisotropy (FA) and mean diffusivity (MD) in corpus callosum and corticospinal white matter tracts were determined obtained using quantitative tractography.

Results: Neonates with prenatal MVM had significantly larger lateral ventricle volumes than matched control subjects (286.4%; p < .0001). Neonates with MVM also had significantly larger intracranial volumes (ICV; 7.1%, p = .0063) and cortical gray matter volumes (10.9%, p = .0004) compared with control subjects. Diffusion tensor imaging tractography revealed a significantly greater MD in the corpus callosum and corticospinal tracts, whereas FA was significantly smaller in several white matter tract regions.

Conclusions: Prenatal enlargement of the lateral ventricle is associated with enlargement of the lateral ventricles after birth, as well as greater gray matter volumes and delayed or abnormal maturation of white matter. It is suggested that prenatal ventricle volume is an early structural marker of altered development of the cerebral cortex and may be a marker of risk for neuropsychiatric disorders associated with ventricle enlargement.

Figure 1

A. Maximum lateral ventricle width in controls and MVM cases (n= 34/group; p < 0.0001). B. Neonates with prenatal MVM have significantly larger lateral ventricle volumes than matched controls (n= 34/group; p < 0.0001). This difference remained significant even when excluding the two outliers in the MVM group (p < 0.0001).

Figure 2

Lateral ventricle size and configuration from representative MVM cases, ranging from largest volume (upper left) to normal volume (lower right).

Figure 3

There was a significant correlation between the prenatal maximum lateral ventricle width on ultrasound and neonatal lateral ventricle volume on MRI for both the normal control (Pearson r = 0.3563; p = 0.0386) and the MVM groups (Pearson r = 0.7482, p < 0.0001).

Figure 4

A. There is a significant difference in the relationship between ICV and cortical gray matter volume in MVM cases compared to controls (homogeneity of slope F=13.15 (,31); p=0.0010), with MVM cases having larger gray matter volumes at larger ICV values. B. There is a significant difference in the relationship between ICV and cortical white matter volume in MVM cases compared to controls (homogeneity of slope F= 7.04 (,31); p=0.0125) with MVM cases smaller white matter volumes than controls at larger ICVs.

Figure 5

A. There was a significant correlation between the lateral ventricle volume and cortical gray matter volume in both the normal control (Pearson r = 0.3539; p = 0.0400) and the MVM groups (Pearson r = 0.5617, p = 0.0005). B. There was a significant correlation between lateral ventricle volume and cortical white matter volume in the normal controls (Pearson 0.3794; p = 0.0269), but not in the MVM group (Pearson 0.0892, p = 0.6160).