Hypoglycemia of Newborn

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Hypoglycemia of Newborn

• Dr. Ilya Rozin

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HYPOGLYCEMIA IN THE NEWBORN INFANT

• Glucose metabolism in the fetus
• Glucose metabolism in the neonate
• Definition of hypoglycemia in the newborn
• Etiology and types of hypoglycemia
• Clinical presentation of hypoglycemia
• Infant of diabetic mother
• Management and outcome

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Glucose metabolism in the fetus

• Maternal glucose is the major substrate delivered
  to the human fetus for energy metabolism.
• Fetal uptake of glucose is regulated by maternal
  glucose concentration.
• Glucose transport concentration gradient
  facilitated diffusion.
• Fetal plasma glucose is 70-80 of mothers.
• When gestational age increases, uterine blood
  flow increases, therefore, blood flow to the
  fetus increases.
• Glucose transport to the fetus is only 40-50 of
  the total uptake by the placenta.

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Glucose metabolism in the fetus

• Insulin in the 8 weeks of gestation and in 13-18
  weeks fetal Insulin response to maternal
  hyperglycemia.
• Insulin stimulates glucose incorporation into
  liver glycogen, acts as growth hormone
• Growth Hormone in the 9 weeks and rapidly
  increased between 11-16 weeks of gestation.
• Fetal GH level is high to maternal plasma.

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Glucose metabolism in the fetus

• Hepatic glycogen content is low in early
  gestation and increases slowly ( between 15-20
  weeks of gestation).
• Glycogenolysis and glycogenesis enzymes are
  present and increase slowly through pregnancy.
• Absence of gluconeogenesis (gluconeogenesis
  enzymes are not active in utero).
• 80 of fetal glucose to energy
• 20 of fetal glucose to lactate, amino acid and
  other means.

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Glucose metabolism in the newbornAt birth

• Discontinuation of maternal substrates and
  nutrient supply need to mobilize glucose or
  other substrates to meet energy requirements.
• Glucose falls (nadir 1-2 hours of age) and
  rises by 2-4 hours in all infants.
• Glucoregulatory hormones (epinephrine,
  norepinephrine, glucagon) rise rapidly, insulin
  decreases (mobilization of glycogen and fatty
  acids).

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Levels of hormones and metabolic fuels change
after birth
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Glucose metabolism in the newborn

• Breast milk provides lactose but not more than
  50 of glucose utilization rate.
• Therefore, neonates are markedly dependent on
  active gluconeogenesis to maintain hepatic
  glucose production.
• Role of elevated Growth Hormone is not defined.
  In first 48-72 hours level is low with elevation
  in the 8 weeks after birth.

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Glucose kinetics in the newborn

• Rates of glucose production and utilization in
  the newborn are between 4-6 mg/kg/min
• Rates are higher in the newborn compared with
  adults due to- Higher metabolic rate- Higher
  brain-to-body weight ratio of the newborn
  brain
• After 2 days, with the introduction of feeding,
  the normal infant maintains plasma glucose at
  40-70 mg/dl (2.5-6 mmol /L).

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Definition of neonatal hypoglycemia

• Statistical approach.
• Clinical approach(Most infants recover after
  birth, lack of correlation with CNS side effects,
  lack of outcome studies, studies based on
  different populations, changes in mothers and
  infants care).
• Most investigators would consider serum glucose
  concentration lt 2.5 mmol/L or 45 mg/dl to be low
  in the first 72 hours of life.
• The definition is the same for term and preterm
  infants.
• Differ to transient and persistent ,symptomatic
  and asymptomatic hypoglycemia.

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Etiology of neonatal hypoglycemia

• I. TRANSIENT HYPOGLYCEMIAA. Changes in
  maternal metabolism 1. Intrapartum
  administration of glucose 2. Drugs
  terbutalin, ritodrin, propranolol
• 3. Diabetes in pregnancy (IDM)B.
  Neonatal problems 1. IUGR/SGA infant
  5. Preterm infant 2. Birth asphyxia
  6. Rh-incompatibility 3. Infection
  7. Hyperviscosity 4.
  Hypothermia 8. Cardiac
  malformations
  9. Iatrogenic causes

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II. Persistent or recurrent hypoglycemia

• A. Hyperinsulinism 1. Beta-cell hyperplasia
  nesidioblastosis -adenoma spectrum,
• 
  sulfonylurea receptor defect. 2. Beckwith-
  Wiedemann Syndrome.
• B. Endocrine disorders1. Pituitary
  insufficiency.2. Cortisol deficiency.3.
  Congenital glucagon deficiency.
• 4. Epinephrine deficiency.
• C. Inborn errors of metabolism1.
  Carbohydrate metabolism galactosemia, fructose
  intolerance, glycogen storage disease,
  gluconeogenesis disorders.2. Amino-acid
  metabolism Maple-syrup urine disease,
  aminoacidopathies3. Fatty-acid metabolism
  carnitine defects, acyl-CoA dehydrogenase
  defects.
• D. Nerohypoglycemia (hypoglycorrhahia)
  defective glucose transport.

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Beckwiths syndrome with glossoptosis
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Incidence of hypoglycemia according to birth
weight and gestational age
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Symptoms and signs of neonatal hypoglycemia

• Abnormal cry
• Apnea, cyanosis
• Feeding difficulties
• Respiratory distress
• Hypothermia
• Hypotonia

• Irritability
• Jitteriness, tremor
• Lethargy, stupor
• Seizures
• Sweating
• Tachycardia

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Infants of Diabetic Mothers

• Macrosomy, visceromegaly, unexplained
  fetal demise

• congenital anomaliesCardiac VSD, TGA, TOF,
  double-outlet..Skeletal and CNS caudal
  regressionGastrointestinal small left colon

• organs and systems abnormalitiesHypoglycemiaH
  eart failure, septal hypertrophyPolycythemiaHype
  rbilirubinemiaHypocalcemiaRenal vein thrombosis

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Infants of Diabetic Mothers
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Maternal hyperglycemia
Fetal hyperglycemia
Fetal Hyperinsulinism
Increased fetal substrate uptake
Activity hepatic enzymes
Metabolic rate
Suppressed production of surfactant
Lipid synthesis
Oxygen consumption
RDS
Macrosomia
Hypoxemia
Cardiomegaly
Synthesis of erythropoietin
Adipose tissue
Stillbirth?
RBC mass - polycythemia
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Blood-work in neonatal hypoglycemia

• Free fatty acid
• Amino acids
• Acetoacetate/beta hydroxybutirate
• Urine Ketones, organic acids, reducing
  substances
• TSH

• Glucose to lab (ASAP, on ice)
• Electrolytes chloride
• Cortisol, growth hormone
• Insulin level
• Blood gases
• Lactate pyruvate
• Ammonia

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Management of neonatal hypoglycemia

• Anticipation in the high-risk groupLGA/SGA
  infants, IDM, acutely ill neonates, preterm
  infant, weight lt2500 or gt 4000 gr.
• Treatment transient vs. persistent
  symptomatic vs. asymptomatic
• Investigation and treatment of the underlying
  cause

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Management of neonatal hypoglycemia

• I. TRANSIENT HYPOGLYCEMIA
• Most are early, Asymptomatic and will recover
  with early feeding
• Symptomatic Hypoglycemia
• Bolus of 2 ml/kg glucose 10. If seizure 4 ml/kg
  of glucose 10.
• All infants, irrespective of cause and age should
  be treated with parenteral glucose infusion 6-8
  mg/kg/min of dextrose 10.
• THE AIM To maintain serum glucose above 45
  mg/dl.
• Therefore Glucose should be monitored
  frequently No response Bolus of 2
  ml/kg glucose 10
  Increase rate or concentration.
• When blood glucose is stable for 4-6 hours
  feeding can be initiated and infusion can be
  weaned.

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Management of neonatal hypoglycemia

• Persistent hypoglycemia
• glucose infusion rate gt 12 mg/kg/min
• Consider a diagnosis of hyperinsulinism, hormonal
  or metabolic disorders.
• Add other drugs
• - Hydrocortisone
• - Glucagon
• - Diazoxide
• - Somatostatin
• - Octreotide
• Pancreatectomy

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Hydrocortisone 1-2 mg/kg/dose 3-4 / day I.V. -???? ???? ?? -???????????, ?????????? -???? ???, ?? ???
Diazoxide Initial 5-10 mg/kg/day in 2-3 dose In Hyperinsulinemia 10-15 mg/kg/day 8-12 hr. P.O. or I.V. -?????? ?? ???? ???? ????? -??????????? -???? ?? ???? -???????, ???????? -???? ???? ??
Somatostatin ( Octreotide ) Initial 1 mcg/kg/dose 4/day with titration. Max. dose 10 mcg/kg/day S/C or I.V. -?????, ????? -?????? ???
Glucagon 0.1-0.3 mg/kg/dose Max. dose 1 mg/dose I.V. I.M. S/C. -?????, ?????? -????????, ????? ???? ?? -?????? ???
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Prognosis and outcome in neonatal hypoglycemia

• Even asymptomatic hypoglycemia in healthy full
  term infants can be associated with abnormal
  neurologic exam (VEP).
• Preterm infants have lower IQ results when
  exposed to recurrent hypoglycemia. They may be
  asymptomatic for long periods and need to be
  monitored.
• IDM with hypoglycemia in the past, suffer lower
  school achievements compared with healthy
  newborns
• Attention should be put when dealing with early
  discharge.
• Brain MRIS damage of posterior hemispheres
  (occipital and parietal).

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Polycythemia

• Hematocrit greatly exceeds normal values for
  gestational and postnatal age.
• Affects approximately 1 to 5 of newborns.
• Many affected infants are asymptomatic.
• Mean Ht and Hb from capillary samples at birth
  are 61 /- 7.4 and 19.3 g/dl /- 2.2.
• The diagnosis is based upon peripheral venous
  samples.

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Polycythemia

• Polycythemia must be distinguished from
  hyperviscosity if greater than 12 centipoise,
  measured at shear rate of 11.5 per sec ( 6
  centipoise at rate of 106 per sec).
• Viscosity and Ht have linear relationship when Ht
  is less than 60.
• Hyperviscosity occurred in only 47 of infant
  with polycythemia.

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Polycythemia

• Incidence
• 1-5 of healthy newborns screened.
• Factors of influence the Ht during the first day
  after birth
• - time delay between birth and clamping of
  the umbilical cord,
• - site of blood sampling,
• - age of the time sampling,
• - method of Ht measurement.

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Polycythemia

• Pathophysiology

Hyperviscosity
Reduced blood flow to organ
Poor tissue perfusion
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Polycythemia

• Causes
• Two major mechanism
• - active ( increased intrauterine erythropoesis)
• - passive ( erythrocyte transfusion )

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Polycythemia

• Causes
• Passive
• Daley clamping of the umbilical cord most
  common.
• Intrapartum hypoxia (increased placental
  transfusion).
• Twin-to-twin transfusion (10-15 of
  monochorionic twin).
• Maternal-fetal transfusion.

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Polycythemia

• Causes
• Active
• Chronic intrauterine hypoxia and placental
  insufficiency
• - SGA.
• - maternal preeclampsia or other vascular
  disorder.
• - maternal hypoxemia due to cardiac or
  pulmonary disorders.
• - drugs propranolol.
• - smoking, high altitude, postterm date.
• - diabetic mother, LGA, Beckwith-Wiedemann
  syndrome.
• Endocrine abnormalities congenital adrenal
  hyperplasia, hypothyroidism, hyperthyroidism.
• Chromosomal abnormalities trisomy 21,18,13.

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Polycythemia

• Clinical features
• Often begin by two hours after birth.
• May delayed to the 2-3 day because of excessive
  extracellular fluid loss.
• Infants with no symptoms by 48 to 72 hours of age
  are likely to remain asymptomatic.
• Signs and symptoms usually due to reduced tissue
  perfusion or associated metabolic abnormalities.

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Polycythemia - Clinical features

• CVS Respiratory- acrocyanosis and sluggish
  peripheral perfusion,
• - plethora,
• - cyanosis
  (17),
• - tachypnea
  distress,
• - heart
  murmur, heart failure and increased vascular
  resistance.

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Polycythemia - Clinical features

• Neurologic effects- irritability,
• - abnormal cry,
• - jitteriness,
• - lethargy,
• - hypotonia,
• - apnea.
• (associated with reduce cerebral blood flow)

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Polycythemia - Clinical features

• Gastrointestinal disorder
• - abdominal distention,
• - poor feeding.
• - NEC ( sometimes).
• ( in 20 of affected infants).

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Polycythemia - Clinical features

• Genitourinary-hematuria, proteinuria, RVT.
• Hypoglycemia- common, in 14-40,
• - Increased Gluc.
  utilization.
• Hyperbilirubinemia-in 1/3 of infants,
• -breakdown and
  increased number of circulated RBC.
• Thrombocytopenia- one report ( 6 of 32 )
• - if Ht gt 70
  - Plt. lt100.K

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Polycythemia

• Diagnosis
• Should be in infant who appear plethoric or who
  have signs or symptoms my be due to polycythemia.
• Ht on a capillary blood sample from a wormed
  heel.
• If Ht capillary gt 65 - repeat on a venous blood.
• Diagnosis of polycythemia if the venous Ht is gt
  65.

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Management of polycythemia

• Controversial uncertain whether intervention
  affect long-term outcome, may be associated with
  some GIT morbidity.
• Asymptomatic newborn with polycythemia do not
  appear to benefit from treatment.
• All polycythemic infant should be monitoring to
  hypoglycemia and hyperbilirubinemia.

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Management of polycythemia

• Asymptomatic
• Ht between 60-70
• - observation, adequate hydration and glucose
  intake (oral intake, body weight, urine output),
• - repeat Ht in 12 24 hours.
• Ht gt 70
• - many clinicians perform Partial Exchange
  Transfusion
• - however, continued observation with
  hydration may be appropriate.

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Management of polycythemia

• Symptomatic
• If Ht gt 65
• - partial exchange transfusion (PET),
• - or observation with I.V. fluids for first
  24-48 hours of age at rate 100 cc/kg/day, with
  glucose rate of 6-8 mg/kg/min.
• If worsening of symptoms PET.

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Partial exchange transfusion

• Reduced Ht without causing hypovolemia.
• Reverses the reduction in cerebral blood flow,
  cardiac index and oxygen transport attributed to
  hyperviscosity.
• Dose not appear to affect long-term outcome.
• My be increased risk of NEC after treatment.

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Partial exchange transfusion

• Exchange volume
• (observed Ht-desire Ht) x blood volume /
  observed Ht.
• Blood volume 80 ml ( to 100 )/kg of BW.
• Desire Ht 45.
• With NaCl 0.9 only.
• Through peripheral or central vein and artery.

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Outcome of polycythemia

• Outcome depend more upon associated condition,
  such as hypoglycemia, or underline disorder, such
  as placental insufficiency.
• Important benefit from PET has not been show.
• Infant with hyperviscosity have poorer neurologic
  outcome (lower IQ, lower score in spilling and
  arithmetical achievement).

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Thank you