NEONATAL

HYPOGLYCEMIA

WHY IS IT IMPORTANT ??
Most common metabolic problem in the NICU/nursery About 15% of SGA and LGAs Often asymptomatic Unrecognised can lead to adverse neurological effects Most cases respond readily to treatment and have excellent prognosis

TRANSITION TO EXTRAUTERINE LIFE

Transplacental diffusion steady state at 2/3rds of maternal glucose levels Abrupt cessation of this supply at birth Reaches a low at 1-2 hrs of life Glycogenolysis and gluconeogenesis gear up and stabilise glucose by 3-4 hrs of life.

THE GREY AREAS

No exact cut off point for adverse neurological outcome Difference in the values obtained based on plasma/blood levels as also the site of sampling.

PATHOGENESIS OF HYPOGLYCEMIC BRAIN

INJURY

OPERATIONAL THRESHOLD
Cornblath suggested glucose levels below which intervention should be considered. Healthy full term 30 to 35 mg/dl on D1 and 45to 50 subsequently Abnormal signs/symptomatic 45 Asymp but at risk 36 Iv glucose indicated for any baby with glucose less than 25

ETIOLOGY
Hyperinsulinism

- IDM/LGA - Birth Asphyxia - Maternal tocolytic therapy - Malpositioned umbilical artery catheter - Beckwith Wiedemann syndrome - Abrupt cessation of conc gluc infusion - Erythroblastosis fetalis - After exchange transfusion - Nesidioblastosis/Islet cell adenoma - Congenital (gene mutations) (ABCC8 / KCNJ11)

Decreased stores - Prematurity - IUGR, Uteroplacental insufficiency Increased utilisation (Perinatal stress) - Sepsis - Shock - Asphyxia - Hypothermia - Respiratory Distress - Post Resuscitation - Polycythemia

CAUSES OF PERSISTENT HYPOGLYCEMIA

Abnormal Carbohydrate Metabolism - Glycogen storage diseases - Galactosemia - Fructose Intolerance Abnormal Aminoacid Metabolism - Maple syrup urine disease - Propionic acidemia - Methyl malonic acidemia - Glutaric acidemia type 2

Endocrine deficiencies - Hypothalamic def./ Hypopituitarism - Adrenal insufficiency - Glucagon deficiency - Epinephrine deficiency

MANIFESTATIONS
Entirely asymptomatic Jitteriness, tremors Irritability; lethargy apathy limpness Poor feeding / vomiting Apnea Weak or high pitched cry Seizures / coma cyanosis

SCREENING OF AT RISK INFANTS

Preterm infants Small for gestation (SGA) Large for gestation (LGA) Infant of diabetic mother (IDM) Sick infants (eg: sepsis, asphyxia, respiratory distress) Post exchange blood transfusion Infants on intravenous fluids and parenteral nutrition Infants whose mothers received beta blockers , oral hypoglycemic agents or intrapartum dextrose infusion

MANAGEMENT
Early initiation of feeding Iv correction required if - not tolerating oral feeds - oral feeding inadequate - symp. Hypoglycemia - asymp with glucose < 25

Iv bolus of 2ml/kg of D10% Followed by continuous infusion at the rate of 6 8 mg/kg/min GIR(mg/kg/min)

=%conc dextrose X fluid vol. (ml/kg/day)/144

Monitor and titrate (central line if >12.5%D reqd to be given) Taper and Inc enteral feeds

REFRACTORY HYPOGLYCEMIA

Refractory hypoglycemia should be suspected if GIR requirements are > 12 mg/kg/min for more than 24 hours

PROLONGED HYPOGLYCEMIA

Prolonged hypoglycemia should be suspected if blood glucose levels remain unstable beyond 5 to 7 days.

CAUSES
Hyperinsulinism Endocrine deficiencies IEMs Mitochondrial disorders

WORK UP
Glucose Insulin Cortisol Serum ketones and FFA levels I/G ratio > 0.3 in hypoglycemia Persistent Hyperinsulinemia - (plasma insulin > 2 U/mL), in presence of documented laboratory hypoglycemia(<50 mg/dL).

WORK UP
Thyroid profile Serum Ammonia Serum Lactate Urine ketones Urine reducing substances Urine aminoacids / organic acids ACTH / GH / Glucagon assay

ADJUNCTS TO DEXTROSE
THERAPY EFFECT DOSAGE Hydrocortisone 5 to 15 mg/kg per day or Prednisone 2 mg/kg per day 30 mcg/kg if normal insulin 300 mcg/kg if increased insulin Corticosteroids

Decrease peripheral glucose utilization

Glucagon

Stimulates glycogenolysis

Diazoxide Somatostatin (longacting: octreotide acetate) Pancreatectomy

Inhibits insulin secretion 15 mg/kg per day Inhibits insulin and 5 to 10 mcg/kg every 6 growth hormone release to 8 h Decreases insulin secretion

SUMMARY OF RECOMMENDATIONS
Neonatal hypoglycemia is a common metabolic disorder and the operational threshold values of blood glucose < 40 mg/dL ( plasma glucose< 45 mg/dL) should be used to guide management. All at risk neonates and sick infants should be monitored for blood glucose levels. Term healthy AGA infants without any risk factors need not be monitored routinely. Screening for hypoglycemia can be done by glucose reagent strips but confirmation requires laboratory estimation by either glucose oxidase or glucose electrode method. Treatment should not be delayed for confirmatory results. Asymptomatic hypoglycemia can be managed with a trial of measured oral feed if blood glucose is > 25 mg/dL and there is no contraindication to feeding. Symptomatic hypoglycemia should be treated with a mini-bolus of 2 ml/kg 10% dextrose and continuous infusion of 6 mg/kg/min of 10%dextrose. Refractory and prolonged hypoglycemia should be suspected and investigated if the glucose infusion requirement is > 12 mg/kg/min for more than 24 hours or the hypoglycemia persists > 5-7 days, respectively. Babies with hypoglycemia should be followed up for neurodevelopmental sequelae.