Background: It remains unclear to what extent midgut rotation determines human intestinal topography and pathology. We reinvestigated the midgut during its looping and herniation phases of development, using novel 3D visualization techniques. Results: We distinguished 3 generations of midgut loops. The topography of primary and secondary loops was constant, but that of tertiary loops not. The orientation of the primary loop changed from sagittal to transverse due to the descent of ventral structures in a body with a still helical body axis. The 1<sup>st</sup> secondary loop (duodenum, proximal jejunum) developed intraabdominally towards a left-sided position. The 2<sup>nd</sup> secondary loop (distal jejunum) assumed a left-sided position inside the hernia before returning, while the 3<sup>rd</sup> and 4<sup>th</sup> secondary loops retained near-midline positions. Intestinal return into the abdomen resembled a backward sliding movement. Only after return, the 4<sup>th</sup> secondary loop (distal ileum, cecum) rapidly "slid" into the right lower abdomen. The seemingly random position of the tertiary small-intestinal loops may have a biomechanical origin. Conclusions: The interpretation of "intestinal rotation" as a mechanistic rather than a descriptive concept underlies much of the confusion accompanying the physiological herniation. We argue, instead, that the concept of "en-bloc rotation" of the developing midgut is a fallacy of schematic drawings. Primary, secondary and tertiary loops arise in a hierarchical fashion. The predictable position and growth of secondary loops is pre-patterned and determines adult intestinal topography. We hypothesize based on published accounts that malrotations result from stunted development of secondary loops.
Soffers, J. H. M., Hikspoors, J. P. J. M., Mekonen, H. K., Koehler, S. E., & Lamers, W. H. (2015). The growth pattern of the human intestine and its mesentery. BMC Developmental Biology, 15(1). https://doi.org/10.1186/s12861-015-0081-x