Overview

Definition:
-Hypoglycemia in infants is defined as a blood glucose level below established thresholds for their postnatal age, which can be indicative of an underlying metabolic, endocrine, or infectious etiology
-Critical sample collection is paramount for accurate diagnosis and timely management, preventing neurological sequelae.
Epidemiology:
-Neonatal hypoglycemia affects 10-15% of all newborns, with higher incidence in preterm infants, infants of diabetic mothers, those with intrauterine growth restriction, and critically ill neonates
-The incidence of persistent or severe hypoglycemia requiring investigation is lower.
Clinical Significance:
-Untreated or prolonged hypoglycemia can lead to impaired brain development, seizures, developmental delay, and long-term neurocognitive deficits
-Prompt and correct biochemical assessment, initiated by appropriate sample collection, guides therapeutic decisions and identifies underlying causes.

Clinical Presentation

Symptoms:
-Jitteriness or tremors
-Irritability or lethargy
-Poor feeding
-Vomiting
-Cyanosis
-Apnea
-Hypotonia
-Temperature instability
-Seizures
-Tachypnea.
Signs:
-Often non-specific and may overlap with other neonatal conditions
-Observe for signs of autonomic instability (pallor, sweating, tremor) and neurological dysfunction (lethargy, hypotonia, seizures).
Diagnostic Criteria:
-Blood glucose below 2.6 mmol/L (47 mg/dL) in term infants in the first 3 days of life, and below 1.7 mmol/L (31 mg/dL) in preterm infants or at any time in the first week of life
-Persistently low values (<2.2 mmol/L or 40 mg/dL) warrant further investigation.

Diagnostic Approach

History Taking:
-Maternal history: diabetes, pre-eclampsia, infections, drug use
-Pregnancy history: SGA, macrosomia, prolonged rupture of membranes, polyhydramnios
-Birth history: birth trauma, perinatal asphyxia, prematurity
-Infant history: feeding pattern, symptoms, duration, previous episodes
-Family history of metabolic or endocrine disorders.
Physical Examination:
-Assess gestational age
-Look for dysmorphic features
-Evaluate for signs of infection (fever, rash)
-Assess hydration status
-Perform a thorough neurological examination for signs of seizure activity, hypotonia, or altered consciousness
-Check vital signs meticulously.
Investigations:
-Point-of-care glucose monitoring using a glucometer is the initial step
-If hypoglycemia is confirmed or suspected, immediate venous blood gas (VBG) or arterial blood gas (ABG) with glucose measurement is crucial
-For further workup: serum lactate, ketones (urine or blood), insulin, C-peptide, cortisol, free fatty acids, amino acids, and acylcarnitine profiles are essential to differentiate etiologies
-Urine metabolic screen and genetic testing may be indicated.
Differential Diagnosis: Hyperinsulinism (e.g., congenital hyperinsulinism), endocrine deficiencies (hypopituitarism, adrenal insufficiency, hypothyroidism), metabolic disorders (glycogen storage diseases, fatty acid oxidation defects, amino acid disorders), intrauterine growth restriction, maternal diabetes, sepsis, polycythemia, transient hypoglycemia due to prematurity or perinatal stress.

Management

Initial Management:
-Immediate feeding (oral or enteral) or intravenous (IV) glucose infusion
-For symptomatic hypoglycemia, initial IV bolus of 10% dextrose at 2 mL/kg is recommended, followed by continuous infusion at 6-8 mg/kg/min, titrating to maintain blood glucose above 2.6 mmol/L (47 mg/dL).
Medical Management:
-If persistent hypoglycemia despite adequate glucose infusion, consider pharmacologic agents
-Glucagon (initial bolus, then infusion) can be used to stimulate hepatic glycogenolysis
-Steroids may be considered for adrenal insufficiency
-Diazoxide or octreotide may be used in cases of hyperinsulinism
-Surgical intervention may be required for persistent hyperinsulinism.
Surgical Management:
-Reserved for specific etiologies, primarily persistent congenital hyperinsulinism unresponsive to medical management
-Options include partial pancreatectomy or genetic therapy.
Supportive Care:
-Continuous glucose monitoring
-Careful fluid and electrolyte balance
-Nutritional support
-Close monitoring for seizures and neurological status
-Management of underlying cause
-Multidisciplinary team approach involving neonatologists, pediatric endocrinologists, and metabolic specialists.

Complications

Early Complications:
-Seizures
-Neurological injury (e.g., hypoxic-ischemic encephalopathy, stroke)
-Cardiac dysfunction
-Renal vein thrombosis.
Late Complications:
-Neurodevelopmental impairment (developmental delay, learning disabilities, attention deficit hyperactivity disorder)
-Visual impairment
-Hearing deficits.
Prevention Strategies:
-Antenatal identification of high-risk pregnancies
-Prompt recognition and initiation of treatment in newborns
-Close monitoring of blood glucose in at-risk infants
-Timely and accurate biochemical investigations to guide management.

Prognosis

Factors Affecting Prognosis:
-Duration and severity of hypoglycemia
-Presence and type of underlying etiology
-Promptness of diagnosis and treatment
-Neurological status at presentation
-Responsiveness to treatment.
Outcomes:
-Most infants with transient hypoglycemia recover fully with prompt treatment
-Infants with persistent or severe hypoglycemia, or those with underlying genetic or metabolic disorders, have a higher risk of long-term neurological sequelae
-Close follow-up is essential.
Follow Up:
-Regular neurodevelopmental assessments
-Audiometry and ophthalmology evaluations
-Developmental pediatrics assessments up to school age
-Ongoing monitoring for recurrence of hypoglycemia or progression of underlying disease.

Key Points

Exam Focus:
-The definition of hypoglycemia in neonates (different thresholds for term vs
-preterm)
-Immediate steps in management including IV dextrose infusion rates
-Key initial investigations (glucometer, VBG/ABG)
-Recognition of symptomatic vs
-asymptomatic hypoglycemia
-Common causes of neonatal hypoglycemia.
Clinical Pearls:
-Always obtain a serum glucose measurement from the same blood sample used for point-of-care testing to confirm findings
-Consider a feeding intolerance or poor latch as early signs of hypoglycemia
-Do not delay IV glucose if symptomatic, even while awaiting laboratory results
-Differentiate between transient causes and persistent disorders requiring specialized workup.
Common Mistakes:
-Relying solely on point-of-care glucometer readings without confirmatory lab tests
-Delayed initiation of IV glucose in symptomatic infants
-Inadequate glucose infusion rates leading to recurrent hypoglycemia
-Failure to investigate the underlying cause of persistent hypoglycemia.