The greatest danger of neonatal hypoglycemia is the neurological damage, which may cause serious neurological sequelae, including mental and motor development delay, visual and hearing impairment, cerebral palsy, and epilepsy. The emergence and severity of the sequelae depend on the degree and duration of neonatal hypoglycemia, as well as other coexisting diseases and treatment. Glucose and oxygen are the most basic substances to maintain brain metabolism, and almost all of the brain’s energy comes from the aerobic metabolism of glucose. After glucose enters brain cells, it is catalyzed by a series of enzymes to produce pyruvate through anaerobic enzymes. Under aerobic conditions, through the tricarboxylic acid cycle, the generated H+ and electrons enter the respiratory chain and interact with oxygen to produce large amounts of adenosine triphosphate (ATP), which is the main source of energy for the brain. Brain tissue is the most complex and highest level of functional activity in the body, as well as the most energy-consuming tissue; unlike the liver, the brain cannot store glycogen and only relies on the continuous blood circulation to supply glucose. When newborns are born, the liver has not yet stored enough glycogen, and the brain has limited glucose from liver glycogenolysis, and is prone to postnatal comorbidities, such as hypoxia and infection, which can consume a lot of energy; therefore, newborns are prone to hypoglycemia. Chronic hyperglycemia in diabetic mothers leads to increased fetal insulin production and pancreatic hyperstimulation, causing high beta-cell proliferation and increased insulin-like activity with hyperinsulinemia, and sudden interruption of maternal supply of glucose after delivery of the fetus but the presence of hyperinsulinemia, which leads to neonatal hypoglycemia. In the newborn, when the blood glucose concentration drops significantly, other substances replace glucose to provide energy to the brain, such as lactate, pyruvate, free fatty acids, glycerol, and keto acids. However, these are not optimal energy donors because most of their precursors (proteins and phospholipids) are structural substances (non-energy donors) that are used as energy-generating stores at the cost of damage to the brain structure and are much less energy-generating than glucose and slower to provide energy. After birth, the neonatal nervous system develops rapidly and has a high energy requirement. When hypoglycemia occurs, the brain cells cannot get enough energy supply and normal metabolism will be affected. When the brain cannot get enough energy from the outside world, lactate formation decreases and the pH value in the brain increases, causing tissue alkalosis; the energy-dependent ion pump malfunctions and cannot maintain the ion gradient inside and outside the cell membrane, causing Na+, Ca2+ inward flow and K+ outward flow, which then causes water molecule inward flow and cell edema; the inward flow of calcium ions activates cellular phospholipase and protease, changing the metabolism of mitochondria , which increases oxygen free radicals; meanwhile, free fatty acid and amino acid metabolism is impaired, and glutamate and aspartate have excitatory neurotoxic effects, which can bind to neural dendritic cells and neurofibrillary network receptors, causing mitochondrial swelling, cell deformation and lysis, and finally causing neuronal necrosis. The relationship between hypoglycemia and brain damage The lower the blood glucose value, the less energy it provides, and the more severe the damage to brain cells. When the blood glucose value is below 1.7 mmol/L, the incidence of brain damage increases greatly. Recently, some American scholars have also suggested that cranial MRI is more severe when the blood glucose value is below 1.7 mmol/L. Whether hypoglycemia can cause brain injury depends on the duration of hypoglycemia in addition to the level of hypoglycemia, but it is certain that the longer the duration of hypoglycemia, the more severe the degree of brain injury.