A 28-year-old woman with pre-gestational Type 2 diabetes (HbA1c 9.2% at conception) presents at 18 weeks gestation. Anomaly scan shows a ventricular septal defect and sacral agenesis. Which feature of sacral agenesis in infants of diabetic mothers (IDM) best identifies the pathophysiological timing and mechanism?

• A Sacral agenesis results from direct teratogenic effect of insulin on axial mesoderm after 8 weeks gestation
• B Caudal regression syndrome results from hyperglycaemia disrupting notochord formation during gastrulation in the 3rd–5th weeks post-fertilization ✓
• C Caudal regression results from fetal hyperinsulinism causing excessive apoptosis in lumbosacral neural tissue
• D Sacral agenesis is a result of vascular disruption from placental insufficiency in the second trimester

Explanation

Caudal regression syndrome (sacral agenesis) in infants of diabetic mothers has a 200-fold increased incidence compared to the general population. The critical window of susceptibility is the 3rd–5th weeks post-fertilization (5th–7th weeks LMP), when gastrulation and notochord formation occur. Hyperglycaemia generates reactive oxygen species that disrupt Wnt signalling and caudal mesodermal differentiation, impairing formation of the sacrum and lower vertebrae. This explains why periconceptional glycaemic control (before conception and in the first 8 weeks) is critical. Fetal hyperinsulinism is not the causative mechanism — it is maternal hyperglycaemia that is teratogenic.

Reference: Williams Obstetrics, 26th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.