bubble_chart Overview

Neonatal hypoglycemia is a common condition in the neonatal period, frequently occurring in premature infants, small-for-gestational-age infants, 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 prompt treatment to reduce the incidence and minimize brain damage.

bubble_chart Etiology

Causes of Hypoglycemia

1. Transient hypoglycemia. Decreased glucose production is seen in: perinatal asphyxia; starvation; neonatal sepsis; cold injury; small for gestational age infants.

Increased glucose consumption due to transient hyperinsulinism: infants of diabetic mothers; neonatal hemolytic disease; Beckwith syndrome; maternal glucose infusion.

2. Persistent or recurrent hypoglycemia. Persistent hyperinsulinism is seen in: nesidioblastosis; islet cell adenoma; other causes of hyperinsulinism. Decreased glucose production is seen in: hormonal deficiencies: growth hormone 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. When glucose infusion is abruptly discontinued, reactive hypoglycemia may occur. Therefore, for post-asphyxia neonates, especially low birth weight infants, glucose infusion should be gradually tapered to avoid reactive hypoglycemia.

Hyperglycemia may result from the following causes:

1. During parenteral nutrition, exogenous glucose infusion fails to suppress endogenous glucose production.

2. Use of corticosteroids in neonates.

3. Iatrogenic hyperglycemia. Excessive glucose infusion, high concentration, or glucose intolerance in neonates.

4. Perinatal asphyxia. Due to catecholamine and glucagon release causing decreased insulin concentration or islet endocrine cell injury and dysfunction, 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 storage in brain tissue is extremely limited, yet the energy demand is enormous. Newborns have highly active metabolism, 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, degenerative changes, and even necrosis. Repeated episodes further exacerbate brain damage. Different parts of the nervous system vary in their sensitivity to hypoglycemia, and the corresponding symptoms appear in the following order: cerebral cortex, cerebellum, subcortical centers [hypothalamus, motor and sensory as well as autonomic (vegetative) lower nerve 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 outward, dilation of cerebral blood vessels, 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.

bubble_chart Clinical Manifestations

1. Hypoglycemia: Neonatal hypoglycemia often presents with atypical or asymptomatic manifestations. A minority of cases may exhibit symptoms such as decreased responsiveness, 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 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, and may also involve convulsions or intracranial hemorrhage.

3. Diagnostic Criteria

(1) Hypoglycemia: According to traditional diagnostic thresholds (whole blood standard).

Ogata ES proposed that plasma glucose <40 mg/dl defines hypoglycemia, noting that plasma glucose values are typically 10–15% higher than whole blood levels (Avery GB. Neonatology 4ed. 1994: 572). In China, there is general consensus that whole blood glucose <2.22 mmol/L (40 mg/dl) serves as the diagnostic threshold for hypoglycemia.

(2) Whole blood glucose ≥7 mmol/L (135 mg/dl) is diagnostic for hyperglycemia.

(3) An inappropriate increase in insulin levels is indicated when the ratio of serum insulin (μU/L) to blood glucose (mmol/L) exceeds 0.3.

4. Blood Glucose Monitoring Methods Clinically, common methods include test strips and micro-blood glucose meters using capillary blood from the heel or venous blood monitoring. Regular monitoring at 1, 3, 6, 9, 12, and 24 hours after birth or upon hospital admission is recommended. However, many primary care hospitals lack the resources for blood glucose monitoring. Tianjin Children’s Hospital proposed using a computer-based discriminant analysis of intrinsic hypoglycemia risk factors (age in days, birth weight, gestational age, infection, and hypoxia) to establish a discriminant formula: Y = -0.18295X1 - 0.90382X2 - 0.0519X3 + 5.6895X4 + 5.10437X5. Neonates scoring Y ≥ -33.80474 are classified as high-risk for hypoglycemia, warranting preventive measures to reduce incidence. Testing on 310 neonates showed high accuracy, with a misjudgment rate of 2.42%, suggesting its potential applicability (Journal of Neonatology, 1996, 11: 54).

bubble_chart Diagnosis

Medical history includes maternal diabetes, pregnancy-induced hypertension, neonatal asphyxia, premature labor, small for gestational age, severe infection, leredema neonatorum, hemolytic disease, polycythemia; history of parenteral nutrition or aminophylline use should prompt regular blood glucose monitoring.

bubble_chart Treatment Measures

1. Hypoglycemia: Blood glucose level <2.22mmol/L (40mg/dl) requires treatment regardless 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 4～6h, adjust the intravenous injection rate, maintain for 24h, then switch to the above glucose solution orally for 1 day; for those who can eat, breastfeed or administer formula via nasogastric tube.

Symptomatic hypoglycemia: Slowly inject 25% glucose intravenously at 2～4ml/kg, at a rate of 1ml/min; continue with 10～12% glucose intravenous drip at 8～10mg/(kg·min), monitor blood glucose regularly, control the speed with an infusion pump, switch to 5% glucose for maintenance after blood glucose stabilizes for 24～48h, gradually reduce the dosage, usually cured in 2～3 days; start 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 5mg/(kg·d) for 2～3 days, intravenous drip; glucagon 0.03mg/kg can be used intramuscularly every 6～12h, while monitoring blood glucose; for hyperinsulinemia, adrenaline can be tried, first use 1:1000 (0.01mg/kg) intradermal injection, if effective, use 1:200 adrenaline in 25% glycerol, administer 0.005～0.01ml/kg orally every 6h. Or use Ephedrine hydrochloride 0.05mg/kg orally every 3h, suitable for infants of diabetic mothers. Diazoxide (which inhibits insulin release) can also be used, 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 replace with soy-based formula.

2. Hyperglycemia Mostly caused by iatrogenic reasons. Treatment methods:

Reduce the amount, concentration, and rate of glucose administration, intake should be <8～12g/(kg·d), especially for premature infants, start with 5% glucose, control the drip rate at 4～6mg/(kg·min). If blood glucose >16.8mmol/L (300mg/dl), urine glucose is positive, or symptoms persist after controlling the infusion rate, insulin supplementation is needed, 0.1～0.2U/kg subcutaneously, repeat every 6～12h if necessary.

Correct dehydration and electrolyte imbalances.

Monitor blood glucose when using aminophylline and corticosteroids.

For transient hyperglycemia, generally no treatment is needed. For severe hyperglycemia or symptomatic cases, immediately administer insulin 0.2U/kg subcutaneously, followed by 1～3U/(kg·d) intravenous drip, along with 1/4～1/5 hypotonic solution, continue 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, feeding should be initiated as early as possible. Sugar water or milk should be given 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, attention should be paid to supplementing amino acids and fat emulsions when providing calories, 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 blood glucose increases, the infusion concentration and rate 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. After resuscitation,