Background Offspring of diabetic mothers have a higher incidence of birth defects. One such defect is sacral agenesis. It is a rare developmental abnormality consisting of the absence of part or all of the sacrum. Offspring of mothers with PGDM have a higher risk of sacral agenesis compared to offspring of mothers with no diabetes. Despite this, there are currently no guidelines to routinely screen offspring of diabetic mothers for sacral agenesis. Research has shown that early intervention for sacral agenesis decreases the risk for future urinary and musculoskeletal complications and thus improves overall prognosis. Objective Determine the utility of prospective spinal ultrasound in infants of mothers with PGDM for the diagnosis of sacral agenesis. Methods This prospective observational pilot study was completed at Women’s and Children’s Hospital in Columbia, Missouri between May 1, 2020 and December 30, 2022. Infants born to mothers with PGDM and with normal spinal examinations were included. A total of 22 mother-infant dyads were enrolled in the study and prospectively screened with spinal ultrasound. The study was registered on ClinicalTrials.gov (Identifier-NCT05033275). Results Twenty-two spinal ultrasounds were performed over the course of this study with three (14%) resulting in abnormal findings that required further imaging. Follow-up with magnetic resonance imaging found one case of tethered cord syndrome. Conclusion Prospective screening in infants of mothers with PGDM found no cases of sacral agenesis but did identify tethered cord syndrome. This finding suggests that risk stratified screening of mothers with diabetes might be a reasonable approach to care.