Purpose and Goal: CNEP # 2041

  • Describe the characteristics of neonatal hypoglycemia.
  • Identify at least two diagnostic strategies for the treatment of neonatal hypoglycemia.

None of the planners, faculty or content specialists has any conflict of interest or will be presenting any off-label product use. This presentation has no commercial support or sponsorship, nor is it co-sponsored.

Requirements for Successful Completion

  • Successfully complete the post-test.
  • Complete the evaluation form.


  • August 2015 – August 2017

Learning Objectives

  • Describe normal glucose homeostasis.
  • Describe the characteristics of neonatal hypoglycemia.
  • Describe the causes and diagnostic strategies for the treatment of neonatal hypoglycemia.


  • Hypoglycemia is a common neonatal metabolic disorder.
  • Incidence is 1.3 – 4.4 out of 1,000 term births.
  • Incidence is 15 – 55 out of 1,000 preterm births.
  • Most healthy newborns experience transient hypoglycemia.
  • Persistent, prolonged, or recurrent hypoglycemia is not normal.
    • The neonatal nervous system is dependent upon glucose.
    • Hypoglycemia can lead to poor neurodevelopmental outcomes.

Fetal Glucose Homeostasis

  • Glucose is a primary source of fetal energy.
  • Fetal glucose needs are met by the placenta.
  • A continuous supply of glucose is provided.
  • Glucose is stored as glycogen.
    • Glycogen is initially stored in the placenta.
    • By 24 weeks, glycogen is stored in the liver.
    • By term, glycogen is stored in cardiac and skeletal muscle.

Neonatal Glucose Homeostasis

  • Glucose is a primary source of neonatal energy.
  • Neonatal glucose needs are met by intermittent feeds.
  • Additionally, fetal glycogen stores are available.
    • By term, glycogen liver stores are twice those of adults.
    • By term, glycogen cardiac stores are 10 times those of adults.
    • Increased glycogen stores balance removal of the placenta.
    • Glycogen stores are depleted within 18–24 hours.
  • Breakdown of stored glycogen is hormone-dependent.
    • Insulin
    • Glucagon
    • Catecholamines
    • Corticosteroids
  • There is a normal surge of hormonal activity at birth.
    • Transient increase of serum glucose levels
    • Followed by decrease in glucose levels within 3-4 hours


  • No uniform standards define neonatal hypoglycemia.
  • It is difficult to define hypoglycemia by a single number.
    • American Academy of Pediatrics definition
      • Glucose levels <45 mg/dL
    • National Consensus Guidelines
      • All symptomatic neonates
        • Glucose levels <45 mg/dL
      • All asymptomatic neonates
        • Glucose levels <40 mg/dL
      • After 24 hours of age
        • Glucose levels <50 mg/dL

Causes of Hypoglycemia

  • Results from lower rate of glucose production than glucose utilization
    • Diminished glucose supply
      • Inadequate glycogen stores
      • Premature infants
      • Growth-restricted infants
    • Impaired glucose production
      • Hyperinsulinism
      • Endocrine disorders
      • Inborn errors of metabolism
    • Increased glucose utilization
      • Sepsis
      • Cold stress
      • Perinatal stress/hypoxia
      • Hyperinsulinism
      • Beckwith-Weiderman syndrome
      • Alloimmune hemolytic disease
      • Neuroglycopenia

Pathophysiology of Hypoglycemia

  • Glucose is the primary energy source for the brain.
  • Glucose is critical for neonatal brain metabolism.
  • Glucose is thought to be just as vital as oxygen.
  • Neonates have a high rate of glucose utilization.
    • The neonatal brain is disproportionally large.
    • The brain uses 30–95% of available glucose.
  • Preterm infants are at higher risk of hypoglycemia.
    • Proportionally larger brain size
    • Markedly decreased glycogen stores

Infants of Diabetic Mothers

  • More than 100,000 infants born each year
  • More than 50% will develop hypoglycemia.
  • Hypoglycemia is related to hyperinsulinism.
    • Fetal exposure to glucose → pancreatic overstimulation
    • Fetal pancreatic overstimulation → hyperinsulinism
    • Fetal hyperinsulinism → decreased utilization of glycogen

Clinical Manifestations

  • Hypoglycemia is often detected by routine monitoring.
  • Neonates are frequently asymptomatic.
  • Signs can be subtle and non-specific.
    • Jitteriness
    • Tremors
    • Irritability
    • Hypotonia
    • Apnea
    • Bradycardia
    • Cyanosis
    • Tachypnea
    • Poor suck
    • Poor feeding
    • Weak cry
    • High-pitched cry
    • Hypothermia
    • Seizures

Identifying Infants at Risk

  • Recognition of infants at risk is critical.
  • All infants at risk should be closely monitored.
  • There are four main groups of at-risk infants.
    • Preterm, post-term and SGA infants
      • Preterm infants have poor glycogen stores.
      • SGA infants have poor glycogen stores.
      • Post-term infants have diminished glucose transfer.
    • Infants of diabetic mothers
      • Hyperinsulinism
    • Extremely low–birthweight infants
      • Glucose-intolerant
      • Insulin-resistant
    • Infants exposed to maternal medications
      • Terbutaline
      • Metformin
      • Valproate

Evaluation and Treatment

  • At-risk infants should be screened within a hour of birth.
    • Pre-feed glucose screens are recommended.
    • Serum glucose confirmation is recommended.
      • Glucose screens are 15% lower than serum levels.
      • RBC metabolism continues in serum samples.
      • Glucose levels may be artificially decreased.
      • Transporting specimens on ice reduces metabolism.
    • Follow-up screens should be every 1 hour until stabilized
    • Once stabilized, every 4–6 hour screening is adequate
  • Treatment goals are prevention and prompt resolution.
  • Adequate oral feeds are essential.
  • Continuous glucose infusions may be necessary.
    • Minimum glucose infusion rate 6 mg/kg/min
  • Glucocorticoid therapy may be required.
    • If glucose infusion rate >12 mg/kg/min for 2 days
    • Hydrocortisone is the preferred drug
    • Prednisone may also be used
  • Glucagon may be required in rare instances.
    • Contraindicated in SGA infants
  • Diaoxide therapy may be required for persistent hyperinsulinism.
  • A pediatric endocrinology evaluation should be obtained.

Laboratory Evaluation

  • Serum glucose
  • Insulin level
  • Cortisol level
  • Growth hormone
  • Thyroid function tests
  • Liver function tests
  • Electrolytes
  • Blood gas
  • Lactate
  • Ammonia
  • Serum amino acids
  • Urine organic acids
  • Urine ketones
  • Urine reducing substances
  • Newborn metabolic screen
  • Carnitine
  • Acetylcarnitine
  • Pyruvate

Long-Term Outcomes

  • Studies have linked hypoglycemia to brain injury.
  • Long-term outcomes
    • Smaller head size
    • Developmental delay
  • Hypoglycemia can lead to poor neurodevelopmental outcomes.


  • Neonatal hypoglycemia is a common neonatal disorder.
  • Infants may present without symptoms.
  • At-risk infants should be monitored closely.
  • Prevention, early detection and intervention is critical.


  1. Noerr, B. 2001. State of the Science: Neonatal Hypoglycemia. Advances in Neonatal Care, 1 (1), P 4-21.
  2. Cowett, R.M. & Loughead, J.L. 2002. Neonatal Glucose Metabolism: Differential Diagnoses, Evaluation, and Treatment of Hypoglycemia. Neonatal Network, 21 (4), p 9-17.
  3. Chan, S.W. 2013. Neonatal Hypoglycemia. Up-To-Date.
  4. Kahler, S.G. 2004. Metabolic Disorders Associated with Neonatal Hypoglycemia. NeoReviews, 5 (9), p e377-e380.
  5. Markham, L.A. 2003. Persistent Hyperinsulinemic Hypoglycemia in Infants. Newborn and Infants Reviews, 3 (4), p 156-167.

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