This document discusses neonatal hypoglycemia. It begins by defining neonatal hypoglycemia and noting the controversial operational thresholds used. It then describes the clinical features and various potential etiologies including increased glucose utilization, decreased production, prematurity, IUGR, and various stressors. The management sections cover prevention, anticipation through screening, diagnosis, treatment primarily with IV dextrose infusion, and adjunct therapies. It notes most cases resolve in 2-3 days but persistent or recurrent hypoglycemia may require further evaluation. The significance of hypoglycemia and potential long-term neurological outcomes are described depending on severity and duration. Long-term neurodevelopmental follow-up is recommended.

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

2. Extremes of
Birth Weight
Neonatal
Hypoglycaemia
Prematurity

3. 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)

4. • 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)

5. • Term breastfed infants
– Can utilise ketones as source of energy in
absence of glucose during transient starvation
– May tolerate low glucose levels better

6. 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

8. 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

9. Infant of diabetic mum
“Cherubic” facies

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

11. ∀ ↓ production/stores
– Prematurity
– Intrauterine growth retardation
– Inadequate caloric intake
Premature
IUGR

12. ∀ ↑ utilisation and/or ↓ production or others
– Stress
• Sepsis (↑ utilisation)
• Shock
• Asphyxia (↓ stores)
• Hypothermia (↑ utilisation)
– Polycythaemia (↑ utilisation by ↑ red cell mass)
– Exchange transfusion
– Inborn errors of metabolism
– 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

13. 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

14. • 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

15. • Diagnosis
– Screening using glucose reagent strips
• Within 2 - 3 hrs after birth & before feeding
(2 - 4 hrly) for 24 - 48 hrs & whenever
symptomatic
– Confirmatory laboratory diagnosis important
• Do not delay treatment while waiting for result
• Analysed promptly to avoid falsely low value due
to glycolysis

16. • 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)

17. – 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
(insulin-secreting tumours)

18. • 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 &
insulin
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

19. 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

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

21. T2 weighted axial MRI at 10 months of age
Boy with isolated hypoglycaemia:
shows parenchymal loss posteriorly with
computed tomography at 6 days of
high signal in the white matter of the
age shows cortical and white matter
parietal and occipital lobes (arrows). Note
low density that is most severe in
thin and atrophic gyri (arrowhead)
the parietal and occipital lobes
Traill, Arch Dis Child 1998

22. Boy with a variant of glycogen T2 weighted axial magnetic resonance image
storage disease type 2b. Computed
at 7 years of age shows marked atrophy in
tomogram at 6 days of age shows low
the parietal and occipital cortex and
density in the cortex and white
underlying cerebral white matter
matter of the parietal and occipital
lobes Traill, Arch Dis Child 1998

23. Outcome
• Varied
• Some have no long term sequelae
• Symptomatic / severe / persistent
hypoglycaemia
– Abnormal neurointellectual development

24. – Cerebral palsy
– Epilepsy
– Cognitive impairment
– Visual problems
– Developmental & behavioural disorders

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