Beyond 18 weeks of gestation, an increased size of the fetal lateral ventricles is reported in most fetuses with open spina bifida. In the first trimester of pregnancy, the definition of ventriculomegaly is based on the ratio of the size of the choroid plexus to the size of the ventricular space or the entire fetal head. However, contrary to what is observed from the midtrimester of pregnancy, in most fetuses with open spina bifida at 11 to 13 weeks of gestation, the amount of fluid in the ventricular system seems to be reduced rather than increased. This study aimed to compare the biometry of the lateral ventricles at 11 0/7 to 13 6/7 weeks of gestation between normal fetuses and those with confirmed open spina bifida. This was a retrospective cohort study that included all cases of isolated open spina bifida detected at 11 0/7 to 13 6/7 weeks of gestation over a period of 5 years and a group of structurally normal fetuses attending at our center over a period of 1 year for the aneuploidy screening as controls. Transventricular axial views of the fetal brain obtained from cases and controls were extracted from the archive for post hoc measurement of cerebral ventricles. The choroid plexus-to-lateral ventricle length ratio, sum of the choroid plexus-to-lateral ventricle area ratio, choroid plexus area-to-fetal head area ratio, and mean choroid plexus length-to-occipitofrontal diameter ratio were calculated for both groups. The measurements obtained from the 2 groups were compared, and the association between each parameter and open spina bifida was investigated. A total of 10 fetuses with open spina bifida were compared with 358 controls. Compared with controls, fetuses with open spina bifida showed a significantly smaller size of the cerebral ventricle measurements, as expressed by larger values of choroid plexus-to-lateral ventricle area ratio (0.49 vs 0.72, respectively; P<.001), choroid plexus-to-lateral ventricle length ratio (0.70 vs 0.79, respectively; P<.001), choroid plexus area-to-fetal head area ratio (0.28 vs 0.33, respectively; P=.006), and choroid plexus length-to-occipitofrontal diameter ratio (0.52 vs 0.60, respectively; P<.001). The choroid plexus-to-lateral ventricle area ratio was found to be the most accurate predictor of open spina bifida, with an area under the curve of 0.88, a sensitivity of 90%, and a specificity of 82%. At 11 0/7 to 13 6/7 weeks of gestation, open spina bifida is consistently associated with a reduced amount of fluid in the lateral cerebral ventricles of the fetus, as expressed by a significantly increased choroid plexus-to-lateral ventricle length ratio, choroid plexus-to-lateral ventricle area ratio, choroid plexus area-to-fetal head area ratio, and choroid plexus length-to-occipitofrontal diameter ratio.