This document discusses neonatal hypoglycemia. It begins by defining hypoglycemia in newborns as a blood glucose level below 40 mg/dL, regardless of symptoms. The main causes of neonatal hypoglycemia include increased glucose utilization due to conditions like hyperinsulinism in infants of diabetic mothers, decreased glucose production due to prematurity or IUGR, or increased utilization combined with decreased production due to perinatal stress. Symptoms of hypoglycemia are non-specific. Management involves prevention by screening at-risk babies, treatment with IV dextrose or adjunctive therapies like glucagon or hydrocortisone if needed, and evaluating for underlying causes if hypoglycemia is persistent or recurrent. Prolong

1. HYPOGLYCEMIA
IN NEWBORN
Dr.David Mendez
Miami Childrens Hospital
Kidz Medical Services

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

11. DIAGNOSIS
• SYMPTOMS
Tremors,jitteriness,irritability,seizures,lethargy, poor
feeding,vomiting ,limpness,weak or high pitched cry
,cyanosis
ASYMPTOMATIC.
• MEASURMENT OF BLOOD GLUCOSE
glucometer- 15% lower than plasma levels
Lab diagnosis-sample obtained and analyzed promptly
(18mg/dl/hr)

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

25. ADDITIONAL TESTS:
Endocrine Evaluation
•
Insulin
•
GH
•
Cortisol/ACTH
•
T4,TSH
•
Glucagon
Metabolic work up
•
ABG/Blood NH3/ lactate
•
Plasma or urine amino acids
•
Urine organic acids
•
Urine ketones/Urine reducing substance

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)

28. • Hypoglycemia
Urine non glucose red substance
Present
Galactosemia
absent
ketones

29. ketones
high
gluconeogenic
defect or
Organic acidemia
low(nonketotic HG)
FA oxidation defect
or
Ketogenic defect
Hyperinsulinism

30. DIFFERENTIAL DIAGNOSIS:
• Sepsis
• CNS disease
• Metabolic
abnormalities(hypocalcemia,hyponatremia,hypernatr
emia,hypomagnesemia,pyridoxine deficiency)
• Adrenal insufficiency
• Renal failure
• Liver failure
• Heart failure

31. THANK YOU!

32. Neonatal
Hypoglycaemia
Dr Varsha Atul Shah
Dept of Neonatal and Developmental Medicine
Singapore General Hospital

33. Extremes of
Birth Weight
Neonatal
Hypoglycaemia
Prematurity

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)

35. • Significant neonatal hypoglycaemia (Whipple’s triad)
• Clinical manifestations
• Coincident low plasma glucose level (laboratory)
• Clinical signs resolve within mins - hrs of establishing
normoglycaemia
• Therapeutic objective
• Raise plasma glucose level > 45mg/dl (2.5mmol/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

39. Aetiology
•
utilisation of glucose: hyperinsulinism
(Hyperinsulinism: inhibit glycogenolysis & gluconeogenesis)
• Infant of diabetic mother (IDM)
• Erythroblastosis
• Beckwith-Wiedemann syndrome
• Islet-cell hyperplasia / hyperfunction
• Insulin-producing tumours (nesidioblastosis, islet-cell
adenoma)
• Maternal drugs (salbutamol, chlorpropamide)
• Abrupt cessation of high-glucose infusions

40. Infant of diabetic mum
“Cherubic” facies

41. Beckwith-Wiedemann
Syndrome
Macrosomia, macroglossia,
omphalocele, hypoglycaemia,
microcephaly

42. •
production/stores
• Prematurity
• Intrauterine growth retardation
• Inadequate caloric intake
Premature
IUGR

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)

48. • Adjunct therapy
• Considered if persistent hypoglycaemia despite glucose
infusion > 10-12mg/kg/min
• Glucagon: stimulates glycogenolysis (adequate glycogen
stores) (AGA/LGA)
• Hydrocortisone: peripheral glucose utilisation,
gluconeogenesis, glucagon effects (prem/SGA)
• Rarely:
• Diazoxide: inhibits insulin secretion
• Somatostatin: inhibits insulin & growth hormone release
• Subtotal pancreatectomy: decreases insulin release (insulinsecreting tumours)

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

51. Symmetric patchy
hyperintensities in occipital
white matter in brain of infant
with transient neonatal
hypoglycaemia
Kinnala Peds 1999

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

55. •
•
•
•
•
Cerebral palsy
Epilepsy
Cognitive impairment
Visual problems
Developmental & behavioural disorders

56. Long Term Management
• Neurodevelopmental follow up to identify sequelae of
neuroglycopenia
• Identify growth deficits