2. INTRODUCTION
• Common metabolic problem
• Blood glucose in newborns are generally lower than
older children & adult
• Fetal glucose level maintained at 2/3 of maternal
B.glucose by transplacental route
• Glucose level fall in Ist 1-2 hrs,lowest value at age of
3 hrs, increase and stabilise by 4 hrs.
• New born – glycogenolysis, gluconeogenesis and
exogenous nutrients.
3. DEFINITION
Defined as a blood glucose level of <40mg % regardless of
gestational age and whether or not symptoms are present
Whipple’s triad:
• low glucose level documented by accurate lab method
• Signs and symptoms of hypoglycemia
• Resolution of signs and symptoms on restoration of
blood glucose levels.
4. ETIOLOGY
• Fetal or Neonatal Hyperinsulinism – ↑utilization of
glucose.
Decreased production or store
Increased utilization and/or decreased production
5. Hypoglycemia of the newborn
Fetal or Neonatal Hyperinsulinism – ↑utilization of glucose.
Babies born to Diabetic mothers(15-25 % GDM,2550% DM)
LGA infants-16%
Erythroblastosis
Islet cell hyperplasia
Beckwith-Weidemann(macrosomia,microcephaly,omphalocoele,macroglos
sia,visceromegaly).
6. Hypoglycemia of the newborn
Insulin producing tumors(islet cell adenoma).
Maternal therapy with tocolytics like
terbutaline,ritodrine, OHA and diuretics
(chlorothiazide)
Glucose infusion through UAC –high glucose into
celiac,SMA—stimulate insulin from pancreas
7. Hypoglycemia of the newborn
Decreased production or store:
Prematurity
IUGR (15% in SGA)
Inadequate calorie intake
Delayed onset of feeding
8. Hypoglycemia of the newborn
Increased utilisation or decreased production:
Perinatal stress
Sepsis/shock/asphyxia/respiratory distress/hypothermia/post resuscitation.
Exchange transfusion
Heparinised blood with low glucose level
CPD blood (relatively hyperglycemic---reactive hypoglcemia
Defects in carbohydrate metabolism
Glycogen storage disease
Fructose intolerance
Galactosemia
9. Hypoglycemia of the newborn
Endocrine deficiency
Adrenal insufficiency
Hypothalamic deficiency
Hypopituitarism
(neonatal emergencies such as apnea, cyanosis, or severe hypoglycemia with or without
seizures, hyperbilirubinemia, and micropenis. )
Glucagon def
Epn deficiency
Defects in amino acid metabolism
MSUD,propionic acidemia,MMA,tyrosinemia
10. Hypoglycemia of the newborn
• Polycythemia
-higher glucose utilization by increased mass of RBC
Maternal therapy with beta blockers
-Prevention of symp stimulation of glycogenolysis
&epinephrine induced increase in FFA
12. MANAGEMENT
• The major long-term sequelae of severe, prolonged
hypoglycemia are mental retardation, recurrent
seizure activity, or both.
• Permanent neurologic sequelae are present in 25–50%
ofbabies with severe recurrent symptomatic
hypoglycemia
• These sequelae are more likely when alternative fuel
sources are limited, as occurs with hyperinsulinemia
• Anticipation and prevention –key to management of
infants with risk factors for HG
13. Routine screening in babies with risk factors
• SGA/Smaller of the discordant twin
• IDM/LGA
• Preterm <35 weeks
• On IVF/TPN
• Prolonged hypoxia
/hypothermia/polycythemia/septicemia/ suspected
IEM
14. •
After exchange tranfusion
•
Rh Hemolytic d/s
•
Babies born to mothers on terbutaline/b-blockers/OHA
•
Symptomatic babies
Screening
•
within 1 hr of birth
•
IDM-0,1,3,6 ,12,18.24,48,72 hrs
•
For 72hrs - risk babies
•
ET-2 hrs after infusing CPD blood
15. • Early feeding with glucose water raises BG only
transiently and asso with rebound hypoglycemia
• Early introduction of breast feeds
o maintain stable BG levels without rebound HG
o keep ketone levels high---alternate fuel during 1st few
days while baby adapts to DBF
o enhances gluconeogenesis
16. • IV therapy
Indications –
intolerance to oral feeds
Symptomatic
oral feeds not maintaining glucose levels
BG level < 25mg/dl
17. o IV glucose through a peripheral line or UVC
o Urgent treatment- 2 ml/kg(200mg/kg) of 10% dextrose over 2-3 min.
o Severe distress – 2-4 ml/kg 25%D(1g/kg glucose) @ 1ml /kg/mt
For eg 2 kg infant-4-8 ml of 25% Dex in 2-4mt
o In asymptomatic baby with low BG levels initial push of conc sugar
→→hyperinsulinism. Therfore, infusion 5-10 ml of 10% D at 1 ml/mt
18. Continuing therapy – based on Glucose Infusion Rate
GIR(mg/kg/min) = % dextrose x ml/kg/day
144
For eg.86 ml/kg/day of 10% D--GIR 6-8
[GIR of 8.33 = 80ml/kg/day of 15%D]
19. •
Monitor BG hourly till euglycemic and thereafter 6th hrly
•
If BG > 40mg%,Continue same and monitor
•
When 2 BG values >50 mg%,wean GIR by 2mg/kg/mt 6th hrly and start oral feeds
Stop infusion when baby is stable @4mg/kg/mt for 12 hr
Monitoring stopped when 2 values on oral feeds >50mg%
20. • If BG < 40 mg%
Repeat bolus & increase GIR by 2mg/kg/mt every 6 hr till euglycemic
If GIR >12 or
HG not resolving by day 7
steroids/glucagon/diazoxide
Further investigations
21. • Check blood glucose after 30 mts of every
change in infusion rate
• Monitoring of glucose levels-to ensure adequate correction of hypoglycemia
-To avoid hyperglycemia---diuresis---dehydration
22. IDM
• <2kg –parenteral therapy in the 1st hour of life
• >2 kg- can be fed hourly, for 3 or 4 feeds ,and then 2
hrly
• As interval increase ,vol ↑
• If by 2 hrs ,despite feeding GRBS< 40 mg%-parenteral therapy
23. Hydrocortisone
• 10mg/kg/day in 2 div doses
• MOA-decrease peripheral glucose utilisation, increase
gluconeogenesis,increase effects of glucagon
• Rapidly tapered off in few days
• Before administration of HC ,obtain blood samples for
insulin and cortisol levels
24. Glucagon
•
Mobilising hepatic glycogen stores
•
Infants with good glycogen stores
•
Not in preterms and malnourished
•
0.025-0.3 mg/kg IM
•
Diazoxide (2-5mg/kg q8h PO) – in persistent hyperinsulinemia
•
Epinephrine
•
Subtotal pancreatectomy
26. • Na /K-adrenal insufficiency
• MRI brain-hypothalamic/pituitary pathology
• CT abdomen-islet cell adenoma
• Genetic testing – to look for mutations
•
27. • Samples to detect insulin levels should be drawn at the
time of low BG
• Criteria for Diagnosing Hyperinsulinism Based on
―Critical‖ Samples
• 1. Hyperinsulinemia (p.insulin >2 μU/mL)
• 2. Hypofattyacidemia (p. FFA<1.5 mmol/L)
• 3. Hypoketonemia (p. β-hydroxybutyrate: <2.0 mmol/L)
• 4. Inappropriate glycemic response to glucagon, 1 mg IV
(rise >40 mg/dL)
34. Definition
• Controversial
• Operational threshold
• Pragmatic approach
• i.e. blood glucose level at which clinical intervention
should be considered
• Indication for action but not diagnostic of disease
• Symptomatic: < 45mg/dl (2.5mmol/L)
• Asymptomatic & at-risk: < 36mg/dl (2.0mmol/L)
36. • Term breastfed infants
• Can utilise ketones as source of energy in absence of
glucose during transient starvation
• May tolerate low glucose levels better
37. Clinical Features
• Non specific
• Apathy, lethargy, irritability
• Hypotonia, limpness
• Sweating, tremors, jitteriness, abnormal cry (weak / high
pitched)
• Hypothermia
• Poor feeding, vomiting
• Apnoea, irregular respiration, respiratory distress,
cyanosis
• Tachycardia, CCF
• Seizures, coma
• Asymptomatic
43. •
utilisation and/or
production or others
• Stress
•
•
•
•
Sepsis ( utilisation)
Shock
Asphyxia ( stores)
Hypothermia ( utilisation)
• Polycythaemia ( utilisation by
• Exchange transfusion
• Inborn errors of metabolism
red cell mass)
• Defect in carbohydrate metabolism
• Glycogen storage disease, fructose intolerance,
galactosemia
• Defect in amino acid metabolism
• Maple syrup urine disease, propionic acidemia, etc
• Endocrine causes
• Adrenal insufficiency, hypothalamic deficiency, congenital
hypopituitarism, glucagon deficiency, epinephrine
deficiency
44. Management
• Prevention
• Antenatal & intrapartum care
• e.g. control of maternal diabetes, causes of prematurity &
IUGR
• Avoid environmental stress e.g. cold
• Early feeding / IV dextrose infusion
45. • Anticipation
• Screening
1. At-risk babies
a. Maternal
e.g. drugs, intrapartum glucose, diabetes, etc
b. Neonatal
e.g. asphyxia / perinatal stress, premature, SGA / LGA, low
birth weight, sepsis, shock, polycythaemia, etc
2. Those with symptoms
Non specific; high index of suspicion
46. • Diagnosis
• Screening using glucose reagent strips
• Within 2 - 3 hrs after birth & before feeding
for 24 - 48 hrs & whenever symptomatic
(2 - 4 hrly)
• Confirmatory laboratory diagnosis important
• Do not delay treatment while waiting for result
• Analysed promptly to avoid falsely low value due to
glycolysis
47. • Treatment
• Aim to maintain plasma glucose > 45mg/dl (2.5mmol/L)
• IV dextrose
• Mini bolus Dex 10% (2ml/kg) followed by infusion
• Central line required for high dextrose concentrations (>
Dex 10%)
• Continued close plasma glucose monitoring to titrate
infusion
• Avoid abruptly decreasing dextrose infusion (rebound
hypoglycaemia)
49. • Most hypoglycaemia resolve in 2 - 3 dys
• Persistent / recurrent hypoglycaemia for > 1 week may
require evaluation for other causes
• e.g. insulin, cortisol, other endocrine & IEM
studies during period of hypoglycaemia
• During a period of hypoglycaemia, a normal infant’s
blood insulin level should be low or absent. If it is very
high suggests hyperinsulinism. It inhibits braeking down
of glyconen
50. Significance of Hypoglycaemia
• Neuronal cell injury, cerebral damage, long term
neurologic sequelae
• No single value below which or duration beyond
which brain injury definitely occurs
• ? Vulnerability of brain of infants of different
gestational ages
• Prevention, prompt treatment important
52. Boy with isolated hypoglycaemia:
computed tomography at 6 days of
age shows cortical and white matter
low density that is most severe in
the parietal and occipital lobes
T2 weighted axial MRI at 10 months of age
shows parenchymal loss posteriorly with
high signal in the white matter of the
parietal and occipital lobes (arrows). Note
thin and atrophic gyri (arrowhead)
Traill, Arch Dis Child 1998
53. Boy with a variant of glycogen
storage disease type 2b. Computed
tomogram at 6 days of age shows low
density in the cortex and white
matter of the parietal and occipital
lobes
T2 weighted axial magnetic resonance image
at 7 years of age shows marked atrophy in
the parietal and occipital cortex and
underlying cerebral white matter
Traill, Arch Dis Child 1998
54. Outcome
• Varied
• Some have no long term sequelae
• Symptomatic / severe / persistent hypoglycaemia
• Abnormal neurointellectual development
