Neonatal hypoglycemia is a common condition in the neonatal period, frequently occurring in premature infants, small-for-gestational-age babies, infants of diabetic mothers, and newborns with hypoxia, asphyxia, neonatal edema, or septic infections. The incidence of this condition is 1–5% in full-term infants, 15–25% in low-birth-weight infants, and approximately 20–30% in cases of neonatal asphyxia. Persistent or recurrent hypoglycemic seizures can lead to severe central nervous system damage, causing impaired energy metabolism in brain cells, cerebral edema, softening, and necrosis, which clinically manifest as intellectual disabilities, cerebral palsy, and other neurological sequelae. Hyperglycemia, primarily iatrogenic, can result in diuresis, dehydration, shock, and intracranial hemorrhage, similarly causing brain damage. Therefore, clinicians should prioritize blood glucose monitoring, emphasizing prevention, early diagnosis, and timely treatment to reduce the incidence and minimize brain injury.

bubble_chart Etiology

Causes of Hypoglycemia

1. Transient Hypoglycemia: Decreased glucose production seen in: asphyxia at birth; starvation; neonatal sepsis; cold injury; small-for-gestational-age infants. Transient hyperinsulinism leading to increased glucose consumption: infants of diabetic mothers; neonatal hemolytic disease; Beckwith syndrome; maternal glucose infusion.
2. Persistent or Recurrent Hypoglycemia: Persistent hyperinsulinism seen in: nesidioblastosis; islet cell adenoma; other causes of hyperinsulinism. Decreased glucose production seen in: hormonal deficiencies: GH deficiency, congenital hypopituitarism; inborn errors of metabolism: amino acid metabolism disorders such as maple syrup urine disease, carbohydrate metabolism disorders such as galactosemia, glycogen storage disease type I.
3. Iatrogenic Hypoglycemia: Rapid glucose infusion may stimulate increased endogenous insulin secretion in neonates, leading to reactive hypoglycemia when glucose infusion is abruptly discontinued. Therefore, for asphyxiated neonates, especially low birth weight infants, gradual tapering of glucose infusion before discontinuation can prevent reactive hypoglycemia.

1. Failure to suppress endogenous glucose production during exogenous glucose infusion in parenteral nutrition.
2. Use of corticosteroids in neonates.
3. Iatrogenic Hyperglycemia: Excessive glucose infusion, high concentration, or glucose intolerance in neonates.
4. Birth asphyxia: Due to release of catecholamines and glucagon, leading to decreased insulin concentration or dysfunction of pancreatic endocrine cells, hypoglycemia often follows hyperglycemia.
5. Transient Diabetes Mellitus: Possibly due to delayed maturation of β-cell function.
6. True diabetes mellitus, rare in neonates.

bubble_chart Pathogenesis

Glucose is the sole energy source for the central nervous system in newborns. The glycogen reserves in brain tissue are extremely limited, yet the energy demand is enormous. Newborns have a high metabolic rate, with brain cells accounting for 13% of their total body weight (compared to only 2% in adults), thus requiring relatively more energy. If blood sugar levels are too low, the metabolic activity of brain cells is affected, leading to reduced ATP production, which directly impacts the Na⁺-K⁺-ATPase. This can cause brain cell swelling of eyelid, degenerative changes, and even necrosis. Repeated episodes further exacerbate brain damage. Different parts of the nervous system vary in their sensitivity to hypoglycemia, with symptoms appearing in the following order: cerebral cortex, cerebellum, subcortical centers [hypothalamus, motor and sensory as well as autonomic (vegetative) lower centers, basal ganglia, etc.]. In severe cases, dysfunction of the medulla oblongata's vital centers can occur, leading to sudden death.

Hyperglycemia results in a hyperosmolar state in the plasma, causing intracellular fluid to leak out, cerebral vasodilation, increased blood volume, and hyperosmolar dehydration of brain cells. In severe cases, this can lead to intracranial hemorrhage. Hyperglycemia can also cause osmotic diuresis, leading to significant loss of water and electrolytes, resulting in dehydration or even shock.

AD

TCM can effectively treat dry eye syndrome, floaters, retinopathy, and various chronic eye diseases

1. Hypoglycemia: Neonatal hypoglycemia often presents with atypical or no symptoms. A few may exhibit symptoms such as lethargy, weak crying, refusal to feed or poor sucking, hypotonia, pallor, hypothermia, irregular breathing, apnea, cyanosis, etc. In severe cases, tremors, convulsions, or unconsciousness may occur. The condition predominantly manifests within the first 1–2 days after birth, and diagnosis can be confirmed with blood glucose monitoring.
2. Hyperglycemia: Early or mild cases may be asymptomatic. Severe cases may present with polydipsia, polyuria, weight loss, sunken eyes, dehydration, or even shock symptoms, and may also involve convulsions or intracranial hemorrhage.

bubble_chart Diagnosis

Diagnostic Criteria

(1) Hypoglycemia: According to the traditional diagnostic value for hypoglycemia (whole blood standard).

Ogata ES proposed that a plasma glucose level <40 mg/dl defines hypoglycemia, with plasma glucose values being 10–15% higher than whole blood (Avery GB. Neonatology 4ed. 1994: 572). Currently, there is general consensus in China that a whole blood glucose level <2.22 mmol/L (40 mg/dl) serves as the diagnostic criterion for hypoglycemia.

(2) A whole blood glucose level ≥7 mmol/L (135 mg/dl) is diagnosed as hyperglycemia.

(3) When the serum insulin level (μU/L) to blood glucose (mmol/L) ratio exceeds 0.3, it indicates inappropriate elevation of insulin levels.

Blood Glucose Monitoring Methods

Clinically, common methods include the paper strip method, micro-blood glucose meters using capillary blood from the heel, and venous blood monitoring. It is recommended to conduct early and scheduled monitoring within 24 hours after birth or upon admission for newborns. However, many primary hospitals lack the resources to perform blood glucose monitoring. Tianjin Children's Hospital proposed using a computer to perform discriminant analysis based on intrinsic hypoglycemia risk factors (age in days, weight, gestational age, infection, and hypoxia), establishing a discriminant formula: Y = -0.18295X1 - 0.90382X2 - 0.0519X3 + 5.6895X4 + 5.10437X5. Using this formula, newborns with a score of Y ≥ -33.80474 are classified as high-risk for hypoglycemia, and preventive measures should be taken to reduce its incidence. Among 310 tested newborns, the accuracy was high, with a misjudgment rate of 2.42%, making it suitable for trial use (Journal of Neonatology, 1996, 11:54).

Maternal history of diabetes, pregnancy-induced hypertension, neonatal asphyxia, premature labor, small-for-gestational-age infants, severe infections, leredema neonatorum, hemolytic disease, polycythemia; history of parenteral nutrition or aminophylline use, etc., should prompt scheduled blood glucose monitoring.

bubble_chart Treatment Measures

1. Hypoglycemia: Blood glucose level <2.22mmol/L (40mg/dl), treatment is required regardless of the presence or absence of symptoms.

Asymptomatic hypoglycemia: Oral administration of 10% glucose at 5–10ml/kg every 2–3 hours; or intravenous injection of 10% glucose at a rate of 6–8mg/(kg·min). Measure blood glucose every 4–6 hours, adjust the intravenous injection rate, and discontinue the IV drip after 24 hours, switching to the aforementioned sugar solution for 1 day. For those able to eat, breastfeed or administer formula via nasogastric tube.

Symptomatic hypoglycemia: Slowly administer 25% glucose intravenously at 2–4ml/kg, infused at a rate of 1ml/min; continue with a 10–12% glucose IV drip at 8–10mg/(kg·min), monitor blood glucose regularly, control the infusion rate with an infusion pump. After blood glucose stabilizes for 24–48 hours, switch to 5% glucose for maintenance, gradually reducing the dosage. Generally, recovery takes 2–3 days. Begin breastfeeding or formula feeding as soon as possible.

Persistent or recurrent severe hypoglycemia: If blood glucose cannot be maintained after 3 days of treatment, add hydrocortisone at 5mg/(kg·d) for 2–3 days via IV drip. Glucagon may be administered intramuscularly at 0.03mg/kg every 6–12 hours, with concurrent blood glucose monitoring. For hyperinsulinemia, epinephrine may be tried, starting with intradermal injection of 1:1000 (0.01mg/kg). If effective, administer 1:200 epinephrine in 25% glycerol orally at 0.005–0.01ml/kg every 6 hours. Alternatively, ephedrine hydrochloride at 0.05mg/kg orally every 3 hours may be used, suitable for infants of diabetic mothers. Diazoxide (which inhibits insulin release) may also be used at 10–15mg/kg per day, divided into 3–4 intravenous or oral doses. For nesidioblastosis or insulinoma, subtotal pancreatectomy is required. For galactosemia, discontinue lactose-containing dairy products and substitute with soy-based formula.

2. Hyperglycemia: Mostly caused by iatrogenic factors.

Treatment methods:

Reduce glucose volume, concentration, and infusion rate. Intake should be <8–12g/(kg·d), especially for premature infants, starting with a 5% glucose concentration at an infusion rate of 4–6mg/(kg·min). If blood glucose >16.8mmol/L (300mg/dl), glycosuria is present, or symptoms persist after adjusting the infusion rate, administer insulin at 0.1–0.2U/kg subcutaneously, repeating every 6–12 hours if necessary.

Correct dehydration and electrolyte imbalances.

Monitor blood glucose when using aminophylline or corticosteroids.

For transient hyperglycemia, treatment is generally unnecessary. For severe hyperglycemia or symptomatic cases, immediately administer insulin subcutaneously at 0.2U/kg, followed by an IV drip of 1–3U/(kg·d), along with 1/4–1/5 hypotonic fluid, for 2–3 days.

bubble_chart Prevention

1. For newborns prone to hypoglycemia, blood glucose should be monitored at 3, 6, 9, 12, and 24 hours after birth to promptly detect hypoglycemia or hyperglycemia.
2. For low birth weight infants and high-risk infants who can feed after birth, early feeding should be initiated. Sugar water or milk should be given starting 2–4 hours after birth. For those unable to feed orally or via nasogastric tube, intravenous glucose infusion should be administered to maintain nutrition.
3. For those receiving parenteral nutrition, when supplementing calories, attention should be paid to supplementing amino acids and fat emulsions, and the glucose concentration should not be too high.
4. For high-risk infants and premature infants, the glucose infusion rate should be controlled to no more than 8 mg/(kg·min), and blood glucose should be monitored. If levels increase, the concentration and rate of infusion should be reduced immediately. However, the infusion should not be abruptly stopped to prevent reactive hypoglycemia.
5. During neonatal asphyxia resuscitation, a 5% glucose concentration should be used.