Objective: The aim of this study was to evaluate the validity of a semiautomated volumetric approach (5DCNS+) for the detailed assessment of the fetal brain in a clinical setting. Methods: Stored 3D volumes of > 1100 consecutive 2nd and 3rd trimester pregnancies (range 15–36 gestational weeks) were analyzed using a workflow-based volumetric approach 5DCNS+, enabling semiautomated reconstruction of diagnostic planes of the fetal central nervous system (CNS). All 3D data sets were examined for plane accuracy, the need for manual adjustment, and fetal-maternal characteristics affecting successful plane reconstruction. We also examined the potential of these standardized views to give additional information on proper gyration and sulci formation with advancing gestation. Results: Based on our data, we were able to show that gestational age with an OR of 1.085 (95% CI 1.041–1.132) and maternal BMI with an OR of 1.022 (95% CI 1.041–1.054) only had a slight impact on the number of manual adjustments needed to reconstruct the complete volume, while maternal age and fetal position during acquisition (p = 0.260) did not have a significant effect. For the vast majority (958/1019; 94%) of volumes, using 5DCNS+ resulted in proper reconstruction of all nine diagnostic planes. In less than 1% (89/9171 planes) of volumes, the program failed to give sufficient information. 5DCNS+ was able to show the onset and changing appearance of CNS folding in a detailed and timely manner (lateral/parietooccipital sulcus formation seen in < 65% at 16–17 gestational weeks vs. 94.6% at 19 weeks). Conclusions: The 5DCNS+ method provides a reliable algorithm to produce detailed, 3D volume–based assessments of fetal CNS integrity through a standardized reconstruction of the orthogonal diagnostic planes. The method further gives valid and reproducible information regarding ongoing cortical development retrieved from these volume sets that might aid in earlier in utero recognition of subtle structural CNS anomalies.