Neonatal hypoglycemia is defined as a blood glucose level below a certain operational threshold, depending on the clinical state and age of the neonate. The main causes include hyperinsulinemic hypoglycemia, decreased production/stores, and increased utilization or decreased production due to perinatal stress, infections, or defects in carbohydrate or amino acid metabolism. Symptoms range from being asymptomatic to neurological or neuroglycopenic symptoms. Management involves frequent feeding or intravenous glucose infusion depending on the severity of hypoglycemia. Recurrent or persistent hypoglycemia requires investigating for underlying causes and treating with drugs like hydrocortisone, diazoxide, or octreotide.

1. Neonatal Hypoglycemia

2. Defintion
 Controversial.
 Operational Thershold:
o Cornblath et al in 2000.
o Concentration of Plasma or Whole blood glucose at
which
Clinicians should consider Intervention, based on
currently available literature.
o Lower than therapeutic goals
o Dependent on clinical state and age.
o Do not define normal or abnormal.
o Provide margin of safety.
o Therapeutic Objective : >45mg/dL

3. OPERATIONAL THRESHOLDS:
Clinical condition Blood glucose level
1 a) Healthy <24hrs first episode
b) Healthy <24hrs persistent
30 to 35mg/dL
45mg/dL
2 Healthy > 24hrs 45 to 50mg/dL
3 Asymptomatic neonate with risk factors 36/dL
4 Neonate with abnormal signs and
symptoms
45mg/dL.
5 Any baby < 20 to 25mg/dL

4.  Whipple’s Triad:
1. Low Blood Glucose Level.
2. Symptoms of Hypoglycemia at the time of low
glucose level.
3. Symptom relief at the time of Hypoglycemia with
intervention.

5. Etiology
 Hyperinsulinemic hypoglycemia
 Large for gestational age infants.
 Decreased Production/Stores.
 Increased utilization/ Decreased production.

6. Hyperinsulinemic Hypoglycemia
 Maternal Hyperglycemia.
 Congenital Genetic: Mutation of genes- ABCC8,
KCNJ11, HNF4A gene.
 Secondary to following conditions:
1. Birth Asphyxia
2. Beckwith- Wiedemann syndrome
3. Abrupt cessation of high glucose infusion.
4. Insulin producing tumors.
5. Erythroblastosis(hyperplastic islets of
langerhans)
6. Malpositioned umblical artery.

7. Decreased Production/Stores
1. Prematurity.
2. Intrauterine growth restriction.
3. Inadequate caloric intake.
4. Delayed onset of feeding.

8. Increased utilization/ Decreased production
 Perinatal Stress:
Sepsis
Shock
Asphyxia
Hypothermia
Respiratory Distress
Postresuscitation.
 Defects in Carbohydrate metabolism:
Glycogen storage disease.
Frutose intolerance.
Galactosemia
 Polycythemia
 Maternal Therapy with BetaBlockers.

9. Increased utilization/ Decreased production
 Endocrine Deficiency:
Adrenal Insufficiency.
Hypothalamic Deficiency.
Congenital Hypopituitarism.
Glucagon Deficiency.
Epinephrine Deficiency.
 Defects in Amino acid metabolism:
Maple Syrup Urine disease.
Propionic acidemia.
Methylmalonic acidemia.
Tyrosinemia.
Glutaric acidemia Type 2.
Ethylmaloni adipic aciduria.

10. Indication for Routine Blood Glucose Screening
1. Infants <2000grams.
2. Infants <_35 weeks.
3. Small for Gestational Age.
4. Large for Gestational Age.
5. Infant of Diabetic Mother.
6. Infants with Rh Hemolytic disease.
7. Mothers receiving therapy with
Terbutaline/Propanolol/Lebatolol/Oral
Hypoglycemic agents
8. IUGR.
9. Any sick neonate (Perinatal
asphyxia/Polycythemia/Sepsis/Shock)
10. Infants on Parenteral Nutrition.

11. Schedule of Blood Glucose
Monitoring
Category of Infants Time Schedule
At Risk Infants( 1 to 8) 2, 6, 12, 24, 48 and 72
Hours
Sick Infants ( Infants with
Sepsis, Asphxia, Shock)
Every 6 to 8 hours.
Stable VLBW infants on
Parenteral Nutrition
Initial 72 hours: Every 6 to 8
hrs.
After 72 hours: Once a day.

12. Methods of Blood Glucose
Estimation
I. Point of Care Glucose Meter:
 Glucose Oxidase method.
 1st Generation: Change in colour by enzymatic
reaction on application of blood drop.
Read by Reflectance meters.
Affected by Hematocrit values, acidosis,
Bilirubin
 Newer Generation: Generate current on reaction of
glucose with enzymes such Glucose Oxidase or
Glucose Dehydrogenase
Amount of Current is proportional to
Amount of sugar in plasma
 Whole blood 10-15% < Plasma Value.

13. Methods of Glucose Estimation
II. Lab Diagnosis:
 Glucose Oxidase Method.
 Glucose Eletrode Method.
 Prompt analysis should be preformed –
Reduction of Glucose concentrate upto 18
mg/dL/hr.
III. Continous Glucose Monitoring:
 Detects using a Sensor.
 Detects many more episodes of low glucose
concentration than blood glucose
measurement.

14. Clinical Manifestations
 Asymptomatic.
 Neurogenic Symptoms:
Jitteriness/Tremors
Sweating.
Irritability.
Tachypnea.
Pallor.
 Neuroglycopenic Symptoms:
Poor suck/Poor feeding.
Weak or high pitched cry.
Change in Level of Consciousness.
Seizures.
Hypotonia.
 Apnea, Bradycardia, Cyanosis, Hypothermia.

15. Management of Neonatal
Hypoglycemia
Hypoglycemia
BGL < 40mg/dL
Asymptomatic Symptomatic

16. Asymptomatic Hypoglycemia
20 to
<40mg/dL
<20mg/dL
Follow Symptomatic
Hypoglycemia protocol
Trial of
Oral
Feeds
Monitor BGL after 1
hour.
> 40mg/dL <40mg/dL
Frequent Feeds
Monitor BGL
Stop after 48 hours
Ensure no feeding difficulty
before Discharge

17. Symptomatic including
Seizures
Bolus of 2ml/kg – 10%
Glucose
IV glucose infusion @ 6mg/kg/min.
Monitor hrly till euglycemia then
6hrly.
BGL >50mg/dL
Stable for 24 hrs on
IVF.
2 values > 50mg/dL
Weaning at 2mg/kg/min every 6
hrs
Increase feeds. Monitor 6 hrly.
Stop IVF when
4mg/kg/min and infant
stable
Stop monitoring when 2
values > 50mg/dL on full
feeds.
BGL < 50mg/dL
Increase glucose
@2mg/kg/min till
Euglycemia
Increase till GIR-
>12mg/kg/min
Refer to Specialist for
further evaluation
Hydrocortisone, Octreotide,
Diazoxide, Glucagon

18. Glucose Infusion Rate
 Neonatal bloody glucose concentration correlate
closely with Glucose infusion rates.
 Normal – 4 to 6 mg/kg/min
 Expressed in mg of glucose/kg body
weight/minute
 Infusion Rate(mg/kg/min) = IV rate(ml/kg/day) * % of
D
144
 % of Dextrose = GIR(mg/kg/min) X 144
IV rate(ml/kg/day)
 5X -25 = amount of 25% D to be added to 100ml of
5%D
 X is the % of Dextrose required.

19. Practical Cues
 Ensure continuous glucose infusion without any
interruption, stopping infusion abruptly - Rebound
Hypoglycemia.
 > 12.5% D – Use central line( Risk of
Thrombophlebitis)
 Persistent Hypoglycemia- check the IV line,
Infusion rate and intravenous fluid preparation.

20. Recurrent or Persistent
Hypoglycemia
 Recurrent episodes of Hypoglycemia or if he fails
to maintain normal BGL despite a GIR of
12mg/kg/min OR Requiring IV glucose for greater
than 7 days.
 Causes:
1. Congenital hypothyroidism
2. Adrenal insufficiency
3. Hyperinsulinemic states
4. Galactosemia
5. Glycogen storage disorders
6. Maple syrup urine disease
7. Mitochondrial disorders.
8. Fatty oxidation defect.

21. Recurrent or Persistent
Hypoglycemia
 Investigations to be done:
1. Serum insulin levels
2. Serum cortisol levels.
3. GH levels
4. Blood Ammonia
5. Blood lactate levels.
6. Urine ketones.
7. Free fatty acid levels.
8. Galatose 1 phosphate uridyl transferase levels.

23. Drugs used in Treatment of Hypoglycemia
Drug Dosage Mechanism of Action Issues
Hydrocorti
sone
5 mg/kg/day in
2 divided
doses.
Reduces peripheral
glucose utilization,
Increases
gluoneogenesis,
Increases effects of
glucagon
Cortisol levels to be
checked before
administration
Diazoxide 5 -8 mg/kg/day
in divided
doses; every 6-
8 hours
Inhibits release of
insulin by acting as a
specific ATP sensitive k
channel agonist in
normal pancreatic beta
cells
Can take upto 5 days
for positive effect to be
seen.
Octreotide 5-
20mcg/kg/day
sc or iv in
divided doses.
Every 6-8
Long acting
somatostatin analog
that inhibits insulin
secretion
Tachyphylaxis

24. Differential Diagnosis
 Sepsis
 CNS disease
 Toxic exposure
 Metabolic abnormalities:
1. Hypocalcemia
2. Hyponatremia or Hypernatremia.
3. Hypomagnesemia.
 Adrenal insufficieny
 Heart Failure
 Renal Failure
 Liver Failure