Maternal diabetes suppresses autophagy in neuroepithelial cells of the developing neural tube which leads to neural tube defect formation. Trehalose treatment reversed autophagy impairment and prevented neural tube defects in diabetic pregnancies. Trehalose resolved homeostatic imbalance by correcting mitochondrial defects, dysfunctional proteins, ER stress, apoptosis, and delayed neurogenesis in the neural tubes exposed to hyperglycemia. Methods of using trehalose as an intervention against hyperglycemia-induced neural tube defects are provided herein.