2.  Hypoglycemia is one of the most common
metabolic problems seen in newborn specially in
sick neonate.
 There is no universal definition for hypoglycemia.
 Various investigators have empirically
recommended different blood lucose levels
(BGLs) that should be maintained in neonatal
period to prevent injury to the developing brain.
 The “normal” range of blood glucose is variable
and depends upon factors like birth

3. weight, gestational age, body stores, feeding
status, availability of energy sources as well as
the presence or absence of disease
 Further, there is no concrete evidence to show
the causation of adverse long-term outcomes by a
particular level or duration of hypoglycemia
Hence, a consensus has been to evolve an
“operational threshold.”

4.  Defined as that concentration of plasma or
whole blood glucose at which clinicians
should consider intervention.
 Operational threshold has been defined as BGL of
less than 40 mg/dL (plasma glucose level less
than 45 mg/dL).
 WHO defines hypoglycemia as BGL of less than
45 mg/dL.

5.  Overall Incidence = 1- 5/1000 live births
◦ Normal newborns – 10% if feeding is delayed
for 3-6 hours after birth
◦ At-Risk Infants – 30%
 LGA – 8%
 Preterm – 15%
 SGA – 15%
 IDM – 20%

6.  Glucose concentration is about 70% of maternal
value
 Enzymes for gluconeogenesis, presented by 3rd
month of gestation.
 Insulin starts production by 12 Wks and increases
third trimester and fetal glycogen deposits begin
ninth week and increases by third trimester
 Glucagon starts production by15 weeks of gestation
 Capable of using alternate substrate as ketone
bodies and activate own glucose production

7.  Newborn has two fold greater basal fasting than
adults
 Gluconeogenesis complements Glycogenolysis
 Increase Catecholamine levels (decrease temp
and loss of placenta) , + glycogenolysis
 Falling glucose causes surge in fetal cortisol
 Surge Glucagon and decrease in plasma insulin
 Lipolysis: FFA and Ketones Sparing glucose
utilization in heart, liver, muscle and brain (k),
producing NADH for Gluconeogenesis.

8.  Brain Glucose uptake is insulin independent,
metabolism supported in part by oxidation ketones
and lactate.

9.  Glucose is the primary fuel for the brain.
 The brain needs a steady supply of
glucose to function normally.
 Glucose is the fetus’s only source of
carbohydrate.
Karlsen, 2006

10. “Compared with adults, infants have a
higher brain to body weight ratio, resulting
in higher glucose demand in relation to
glucose production capacity”.
“Cerebral glucose utilization accounts for
90% of the neonate’s glucose
consumption”.

11.  Fetal plasma glucose is 60 – 80% of the
maternal glucose level.
 The fetus stores glucose in the form of
glycogen (liver, heart, lung, and skeletal
muscle).
 Most of the glycogen is made and stored
in the last month of the 3rd trimester.

12.  The fetus has limited ability to convert
glycogen to glucose and must rely upon
placental transfer of glucose to meet
energy needs.
 When the infant is born, the cord is cut
and so is the major supply of glucose!

13.  The transition from fetus to newborn
creates a significant energy drain on the
newborn.
 The newborn is now required to meet
increased metabolic demands while
changing the energy source from a
placenta-supplied source to an external
food source.

14.  1 Low birth weight infants (<2000 grams)
 2 Preterm infants (<weeks)
 3 Small for gestational age infants
(SGA) : birth weight <10th percentile
 4 Infant of diabetic mothers (IDM)
 5 Large for gestational age (LGA)
infants: birth weight >90th percentile*
 6 Infants with Rh-hemolytic disease

15.  Infants born to mothers receiving therapy
with terbutaline/propranolol/lebatolol/oral
hypoglycemic agents
 8 Infants with morphological IUGR
 9 Any sick neonate such as those with
perinatal asphyxia, polycythemia, sepsis,
shock etc
 10 Infants on total parenteral
nutrition

16.  Secondary to Increased utilization of
glucose
 Inadequate supply of glucose
 Combination of two
Karlsen, 2006

17.  The most common cause is neonatal hyperinsulinemia-
 Self limiting hyperinsulinemia-
 IDM
 Rhesus hemolytic disease
 PNA
 IUGR
 Antenatal administration of Thiazide Diuretics
 Iatrogenic
 Beckwith-Wiedemann Syndrome
 Congenital Hyperinsulinemic hypoglycemia

18.  Three possible mechanism may cause failure of glucose
production-
 Reduced availability of gluconeogenic
precursor-limited availability of
glycogen.i.e.Preterm,IUGR,HIE,Inadequate substrate
intake
 Reduced activity of enzyme-sepsis,CHD,Cold
injury,Preterm
 Impaired counter-regulatory hormone-
Preterm,IUGR,Maternal medication with b- blocker

19.  Glucose crosses the placenta
 Insulin does not cross the placenta
 Results – fetus produces own insulin in
the presence of elevated glucose from the
mother
 Excessive formation of oxygen radicals
that damage the mitochondria
 This increase in oxidative stress results
disrupts vascularization of the developing
tissues.

20. Hyperglycemia alters the expression of
regulating genes leading to altered
cellular mitosis and the normal timing of
cell death. Excessive cell death results in
fetal anomalies.
 Caudal regression syndrome
 Hydronephrosis
 Renal agenesis
 Micropenis
 Cystic kidneys
 Intestinal atresias

21.  Anencephaly
 Spina bifida
 Caudal dysplasia
 CNS damage as a result of
◦ Birth trauma (macrosomia)
◦ Glucose and electrolyte abnormalities
◦ Perinatal asphyxia

22.  RDS
 CHD
◦ VSD
◦ Asymmetric septal hypertrophy
◦ Thickened myocardium
◦ Transposition of the greater vessels
 Polycythemia and vascular sludging

23.  Transient
 Persistent

24.  Insufficient calorie intake or delayed onset of feeding
 LGA,SGA,IUGR Infants
 Infant of gestational or IDM
 Postmature ,Premature Infant
 Infection ,Sepsis
 shock
 Respiratory distress
 Perinatal stress
 Asphyxia/HIE
 Hypothermia/Hyperthermia

25.  Polycythemia
 Erythroblastosis Foetalis

26.  Defined as hypoglycaemia lasting for more than 7
days or infant who require higher amount of
glucose(>10-12mg/kg/min) to maintain normal
glucose level for over a week.
 Causes –
 Hyperinsulinism –Congenital,B Cell
Adenoma,Syndrome(BW,Soto)
 Endocrine Disorder-GH Def,Cong Hypopituitarism
 Inborn Error of metabolism-
Galactosemia,GSD,Fatty Acid oxidation
defect,Disorder of amino acid metabolism

27. At risk group Presentation No. of Patient
Preterm Low substrate
Immature hormone
Fluid restriction
Feeding difficulty
Poor Temp Control
IUGR Low substrate
Immature hormone
Fluid restriction
Feeding difficulty
Poor Temp Control
IDM Hyperinsulinism

28. At risk group Presentation No. of Patient
Perinatal Asphyxia Low substrate
Exhausted Stress Response
Enzyme Dysfunction
Fluid restriction
Feeding difficulty
Hyperinsulinism
Septicemia Exhausted Stress Response
Enzyme Dysfunction
Fluid restriction
Feeding difficulty
Inborn error of Metabolism Defect of enzyme of
Glycogenesis,Glycogenolysis,Fatty
acid oxidation

29. Schedule of blood glucose
monitoring
Category of infants Time schedule
SAt risk neonates 2, 6, 12, 24, 48, and 72 hrs
ex distribution:
Sick infants (Infants with sepsis,
asphyxia, shock during active phase of
illness. Once the underlying condition
is under control, frequency of
screening can be reduced or
Every 6-8 hrs (individualize as needed)
Stable VLBW infants on
parenteral nutrition
Initial 72 h: every 6 to 8 hrs
After 72 hr: once a day

30. Clinical signs associated with
hypoglycemia
 Asymptomatic
Symptomatic: A smaller proportion of infants with
hypoglycemia can be symptomatic. Clinical signs of
hypoglycemia are variable and may include stupor,
jitteriness, tremors, apathy, episodes of cyanosis

31. Cont..
convulsions, intermittent apneic spells or
tachypnea, weak and high pitched cry, limpness
and lethargy, difficulty in feeding, and eye
rolling.
Episodes of sweating, sudden pallor,
hypothermia and cardiac arrest have also been
reported.

32. Evaluation
History
Does the mother has any risk factor-
IDM,Preeclampsia, receiving I/V glucose during
delivery or on oral terbutaline,oral hypoglycemic drug
If infant at risk for hypoglycemia-
Prematurity,hypoxia/Asphyxia,hypothermia,Illness(re
spiratory distress,sepsis)
How much glucose is pt receiving
Is there any symptoms of hypoglycemia,poor
feeding ,lethargy,apnea,jitteriness,seizure
H/o consanguinity

33. Physical examination
Irritability,Lethargy
Tachypnea
Cyanosis
Eye rolling
Weak or high pitched cry
Exaggerated moro reflex

34. Features of underlying cause
Signs of sepsis or shock
IDM-
Macrosomic,large,plump,puffy,plethoric,Congenital
malformation(GIT,Heart ,Renal, CNS Anomaly)
Hypopituitarism-Midline defect and micropenis
Galactosaemia,Intra-uterine infection-Catarract
Beckwith-Wiedemann Syndrome- Facial
dysmorphism ,Liver may be enlarged

35. CONT..
Congenital Adrenal Hyperplasia-Ambiguous genitalia
Maple Syrup Urine Disease-Smell of urine
Anthropometry-LGA/SGA

36. Investigation
Transient Hypoglycemia:
S.Glucose level
CBC to rule out sepsis & Polycythemia
S. electrolyte
Persistent Hypoglycemia:Aim is to determine
hyperinsulinemia
Initial study: S.Glucose and insulin
S.Ketone
S.Lactate
S.Ammonia

37. Other tests:
S.PH
Cortisol & ACTH(Adrenal insufficiency)
Growth hormone level
T4 &TSH
Urinary Ketone and reducing substances or amino
acid and organic acid

39. MRI Changes

40. hyperintense lesions in the IC and CR, with reduced
ADC values. B, Follow-up DWI obtained 4 days after
symptom improvement shows that the hyperintense
lesions have disappeared, with normalization of ADC
values.

41. Management
Hypoglycemia(Blood sugar <45mg/dl)
Symptomatic Asymptomatic

42. Figure 1: Algorithm for management of neonatal hypoglycemia
(Asymptomatic)4,5
ASYMPTOMATIC
25-45mg/dl <25mg/dl
Trial oral feeding
Monitor blood sugar
after 30 to 60 mins
<45mg/dl >45mg/dl
Follow
symptomatic
hypoglycemia
Monitor blood glucose 6-8 hrly
Stop after 48 hrs
Follow symptomatic
hypoglycemia

43. Figure 2: Algorithm for management of neonatal hypoglycemia (Symptomatic)
Symptomatic
Hypoglycemia
Bolus of 2ml/kg 10% dextrose
I/V Glucose infusion@6mg/kg/min,monitor 30-60min
interval till euglycaemic& then 6 hrly
Blood sugar>45mg/dl Blood
sugar<45mg/dl
Increase glucose infusion rate@2mg/kg/min
upto 12mg/kg/min
Refer to specialist center
Stable for 24 hrs on i/v
fluid
Weaning at 2 mg/kg/min every 6
hrs,monitor 6 hrly,increase oral feed
Stop I/V Fluid when rate
is 4mg/kg/min

44. Practical points
Useful formulae for Calculating GIR (Glucose
Infusion Rate):
(a) Infusion rate (mg/kg/min) = [ IV rate(ml/kg/day)x % of
dextrose ] / 144
(b) GIR (mg/kg/min) = % of dextrose being infused x rate
(mL/hr)/ body weight (in kg) x 6
(c) Infusion rate = Fluid rate (mL/kg/day) x 0.007 x % of
dextrose infused (mg/kg/min)

45. Cont..
When IV bolus glucose is indicated?
Symptomatic hypoglycemia
Blood glucose <1.4 mmol/L
Indication of IV fluid in hypoglycaemia:
Symptomatic
Blood glucose < 1.7 mmol/L
Inability to tolerate oral feeding ( vomiting)
Persistent hypoglycaemia despite adequate fluid & glucose
management

46. Resistant Hypoglycemia
I
If hypoglycemia persist despite high glucose delivery rate
than drug should be started-
Hydrocortisone 5 mg/kg/day IV or PO in two divided
doses for 24 to 48 hrs
 Diazoxide can be given orally 10-25 mg/kg/day in three
divided doses
 Octreotide (synthetic somatostatin in dose of 2-10
μg/kg/day subcutaneously two to three times a day.
 Glucagon

47. Specific Treatment
Congenital Hypopituitarism
Metabolic Defect-GSD,Galactosemia

48. Outcome
The outcome of hypoglycemia is determined by
factors like, duration, degree of hypoglycemia, rate of
cerebral blood flow, cerebral utilization of glucose,
and also co-morbidities.
It is unlikely that brief self limiting episodes are of
neurological significance.
Adverse neurological signs have been associated with
longterm outcome.
 Special attention should be paid to neuro-
developmental outcome, overall IQ, reading ability,
arithmetic proficiency and motor performance.

49. Prevention
Increase awareness of conditions that predispose
an infant to hypoglycemia
Early screening of at-risk infants
Early and frequent feedings
Maintain temperature

50. Thank You