HYPOGLYCEMIA

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

• Fetal or Neonatal Hyperinsulinism – ↑utilization of

glucose.

 Decreased production or store

 Increased utilization and/or decreased production

 Hypoglycemia of the newborn

 Fetal or Neonatal Hyperinsulinism – ↑utilization of glucose.

 Babies born to Diabetic mothers(15-25 % GDM,25-

50% DM)

 LGA infants-16%
 Erythroblastosis
 Islet cell hyperplasia
 Beckwith-Weidemann-
(macrosomia,microcephaly,omphalocoele,macroglos
sia,visceromegaly).
 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
 Hypoglycemia of the newborn

 Decreased production or store:

 Prematurity

 IUGR (15% in SGA)

 Inadequate calorie intake

 Delayed onset of feeding

 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
 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
 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
 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)
 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
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
• 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

• 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
• IV therapy
Indications –
 intolerance to oral feeds
 Symptomatic
 oral feeds not maintaining glucose levels
 BG level < 25mg/dl
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
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]
• 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%

• 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
• 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
 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
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
 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
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

• Na /K-adrenal insufficiency

• MRI brain-hypothalamic/pituitary pathology

• CT abdomen-islet cell adenoma

• Genetic testing – to look for mutations

•
• 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)
• Hypoglycemia

Urine non glucose red substance

Present absent

Galactosemia ketones
 ketones

high low(nonketotic HG)

gluconeogenic FA oxidation defect

defect or or
Organic acidemia Ketogenic defect
Hyperinsulinism
DIFFERENTIAL DIAGNOSIS:

• Sepsis
• CNS disease
• Metabolic
abnormalities(hypocalcemia,hyponatremia,hypernatr
emia,hypomagnesemia,pyridoxine deficiency)
• Adrenal insufficiency
• Renal failure
• Liver failure
• Heart failure
THANK YOU!
 Neonatal
Hypoglycaemia

Dr Varsha Atul Shah

Dept of Neonatal and Developmental Medicine
Singapore General Hospital
 Extremes of
Birth Weight

Neonatal
Hypoglycaemia

Prematurity
 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)
• 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)
• Term breastfed infants
• Can utilise ketones as source of energy in absence of
glucose during transient starvation
• May tolerate low glucose levels better
 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
 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
Infant of diabetic mum
“Cherubic” facies
Beckwith-Wiedemann
Syndrome
Macrosomia, macroglossia,
omphalocele, hypoglycaemia,
microcephaly
• production/stores
• Prematurity
• Intrauterine growth retardation
• Inadequate caloric intake

Premature

IUGR
• 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
 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

• 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

• 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
• 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)
• 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)
• 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
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

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

• Varied

• Some have no long term sequelae

• Symptomatic / severe / persistent hypoglycaemia

• Abnormal neurointellectual development
• Cerebral palsy
• Epilepsy
• Cognitive impairment
• Visual problems
• Developmental & behavioural disorders
 Long Term Management

• Neurodevelopmental follow up to identify sequelae of

neuroglycopenia

• Identify growth deficits