Transcript Neonatal Hypoglycemia

NEONATAL
HYPOGLYCEMIA
Definition
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The numerical definition varies from institution to
institution:
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Numbers based on population studies of plasma glucose
concentrations during first 48-72 hours of life with
hypoglycemia defined as a plasma glucose level more than
2 SD below the population mean
Most institutions use plasma glucose <40mg/dl on the
1st day of life and less than 40-50mg/dl after 24 hours
of life
Physiologic definition: when glucose supply for cells is
inadequate to meet glucose demands
Incidence
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Estimated to be 10% of live births if first feeding is
delayed for more than 3-6 hours after birth
Percentage is even higher for at-risk populations:
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Preterm infants
SGA infants
LGA infants
Infants of diabetic mothers
Pathophysiology
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Newborns have high brain-to-body weight ratio -> higher
glucose demand
Impaired establishment of normal glucose homeostasis
during transition from intrauterine to extrauterine life ->
hypoglycemia
Normal glucose homeostasis requires supply to meet
demands
Supply is dependent on adequate stores of glycogen,
gluconeogenesis precursors, functioning hepatic enzymes,
and a functioning endocrine system
Demands depend on the metabolic rate of the infant, which
can be increased in times of stress (i.e. sepsis, asphyxia)
Clinical Manifestations
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Asymptomatic
Tachypnea
Apnea
Respiratory distress
Tachycardia
Bradycardia
Jitteriness
Lethargy
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Hypotonia
Weak suck
Temperature instability
Seizures
Etiology
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Diminished glucose production
Increased glucose utilization from hyperinsulinemia
Increased glucose utilization without
hyperinsulinemia
Metabolic Disorders
Endocrine Disorders
Other
Diminished Glucose Production
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Premature infants have diminished reserves because
glycogen is deposited during the 3rd trimester of
pregnancy
Infants with intrauterine growth restriction (IUGR)
and who are SGA have reduced glycogen stores
because of:
 Low
intrauterine insulin levels
 Chronic intrauterine hypoxia
Increased Glucose Utilization Due to
Hyperinsulinemia
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Infant of a diabetic mother
Maternal intrapartum treatment with glucose
Beckwith-Wiedemann syndrome
Insulinoma
Infant of a Diabetic Mother
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Intermittent maternal hyperglycemia -> fetal
hyperglycemia and hyperinsulinemia ->
hypoglycemia once intrauterine glucose supply from
mother is interrupted
Hypoglycemia occurs in 27% of infants of diabetic
mothers (IDMs)
Happens in the first few hours of life
Most common in macrosomic IDMs
Premature &/or SGA IDMs are also at higher risk
Beckwith-Wiedemann Syndrome
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Fetal overgrowth
syndrome with
characteristic features:
Macroglossia
 Growth >90%
 Abdominal wall defects
 Ear creases/pits
 Renal abnormalities
 Hemi-hyperthrophy
 Hyperplasia of organs
(such as the pancreas)
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Beckwith-Wiedemann Syndrome
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Incidence: 1 in 15,000 births
Etiology: Sporadic mutation (85%), AD (15%)
50% have transient hypoglycemia caused by
hyperinsulinemia from hyperplasia of the pancreas
Increased risk for malignancy:
Wilms tumor, hepatoblastoma, neuroblastoma,
gonadoblastoma
 Monitored with abdominal US and alpha-fetoprotein q6months
until 6 y/o
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Insulinoma
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Tumor of the pancreas
that produces too much
insulin
Very rare in children
Most are benign tumors,
only about 5-10% are
malignant
Treatment is surgical
If unable to surgically
remove, treat with
diazoxide or octreotide
to reduce insulin secretion
Increased Glucose Utilization Without
Hyperinsulinemia
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States of stress such as hypothermia, perinatal
asphyxia, sepsis, and heart failure increase usage
and depletion of glycogen stores
Polycythemia - increased utilization of glucose by
the increased mass of RBCs
Metabolic Disorders
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Inborn errors of metabolism:
 Defects
in carbohydrate metabolism
 Glycogen
Storage Disease
 Glycogen Synthase Deficiency
 Galactosemia
 Fructose Intolerance
 Defects
in amino acid metabolism
 Maple
Syrup Urine Disease
 Propionic Acidemia
 Methylmalonic Acidemia
 Defects
in ketogenesis and fatty acid oxidation
Endocrine Disorders
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Deficiency or malfunctioning of the hormones that
regulate glucose homeostasis:
Cortisol
 Growth hormone
 Glucagon
 Epinephrine
 Thyroid
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These could be associated with hypothalamic,
pituitary, or adrenal insufficiency
Other Causes
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Maternal drugs such as terbutaline, labetalol,
propranolol -> inhibit glycogenolysis and
gluconeogenesis
Neurohypoglycemia:
GLUT1 transport protein facilitates glucose diffusion across
blood vessels into the brain and CSF
 Deficiency in GLUT1 results in low CSF glucose, but blood
glucose levels are normal
 Rare disorder that presents as 2-3 months with seizures,
developmental delay, and acquired microcephaly
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Evaluation
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Blood glucose should be monitored for infants at risk for
hypoglycemia:
Premature infants
 SGA infants
 LGA infants
 IDMs
 Infants whose mothers were treated with beta adrenergic
agents or beta blockers
 Infants under stress requiring more intensive care (i.e. sepsis,
asphyxia)
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Evaluation
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Monitor glucose within first 1-2 hours of life or with
signs consistent with hypoglycemia
Surveillance should be continued in infants with
glucose <40 until feedings well established and
levels have stabilized
Low Chemstrips (glucose oxidase reagent strips for
rapid screening) should be confirmed with serum
glucose level processed by the lab
Evaluation
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Determining Etiology:
 Consider
prenatal/perinatal history
 Check growth parameters
 Perform a careful physical exam
 Screen for sepsis if suspected
Evaluation
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If hypoglycemia persists for >1 week, endocrine and metabolic
disorders should be suspected
 Consult endocrinology
 At the time of hypoglycemia, obtain:
 ACTH/cortisol levels
 Growth hormone levels
 Insulin levels
 Free fatty acids
 Ketones
 Pyruvate
 Lactate
Evaluation
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following should also be obtained, but can be
obtained at anytime:
 TSH/T4 levels
 Serum amino acids
 Urine organic acids
 Acylcarnitine profile
Management
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Anticipation and prevention is key
In infants who are premature or too ill to feed,
begin parenteral glucose infusion at a rate of at
least 6mg/kg/min
Glucose (mg/kg/min) = (% glucose in solution x 10)
x (rate of infusion per hour) / (60 x weight in kg)
Healthy asymptomatic infants
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Try feeding orally with either formula, breastmilk, or
D10W
Use of formula or breastmilk better than D10W
because they provide carbohydrates as well as protein
and fats that are metabolized more slowly to provide a
sustained supply of substrate
Recheck glucose in 20-30 mins after the feeding and
continue to feed q2-3 hrs
Blood glucose should be followed before each feed for
12-24 hours
Symptomatic infants or infants with very low
glucose concentrations
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Start parenteral glucose infusions on:
 Symptomatic
infants
 Infants with a glucose of <20-25
 Infants who do not tolerate enteral feedings
 Infants whose blood sugar remains <40 after a trial of
oral feeding
Symptomatic infants or infants with very low
glucose concentrations:
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Start with a bolus of 2-4ml/kg of D10W
Then begin a glucose infusion of at least 6mg/kg/min
Check blood glucose 20-30 mins after bolus to determine
if another bolus is needed, and adjust rate of dextrose
concentration to maintain plasma glucose >45mg/dl
Follow blood glucose every 1-2 hours until stable, then
can space out monitoring as needed
When the glucose concentration is stable for 12-24 hrs,
the glucose infusion rate can be tapered slowly by 1020% each time the feeds are advanced and the preprandial blood glucose is >50-60 mg/dl
Persistent Hypoglycemia (> 7 days)
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Corticosteroids stimulate gluconeogenesis and reduces
peripheral glucose utilization
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should be considered in infants who remain hypoglycemic
after 2-3 days of glucose infusion of >12mg/kg/min
Glucagon can also be used during severe hypoglycemia
as a temporizing measure in infants with adequate
glycogen stores (i.e. NOT in SGA or premature infants)
Diazoxide/Somatostatin/Octreotide inhibits insulin
release for those with persistent hypoglycemia and
hyperinsulinemia
Persistent Hypoglycemia (> 7 days)
Human growth hormone for infants with growth
hormone deficiency
 Nifedipine – case reports have shown some
success with few side effects
 Subtotal pancreatectomy for hyperinsulinemia
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 hypoglycemia
recurs in up to 1/3 of patients
 40-60% develop DM later in life
Prognosis
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Symptomatic hypoglycemia can result in brain injury
Most common sequelae are:
Disturbances in neurological development and intellectual
function
 Motor deficits (spasticity and ataxia)
 Seizures
* May be related to the underlying etiology of the hypoglycemia
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There is inconclusive evidence on the effect of
asymptomatic hypoglycemia on neurodevelopment