neonatal hypoglycemia arif

NEONATAL HYPOGLYCEMIA

Mohd. Arif Khan1st year PG student

Department of Pediatrics

INTRODUCTION

• Common metabolic problem encountered in nicu.

• Blood glucose levels (BGL) in newborns are generally lower than older children & adult.

• Fetal glucose level is maintained at 2/3rd of maternal Blood glucose by trans-placental route.

• BGL falls in First 1 to 2 hrs, then increases and stabilizes by age of 3 to 4 hrs.

DEFINITION

•There is no universal definition of neonatal hypoglycemia.

•BGL range varies with certain factors like gestational age, birth-weight, feeding status, body stores and presence/absence of a disease.

•WHO defines hypoglycemia as BGL below 45mg/dl.

•Cornblath in 2000, recommended the use of operational threshold for hypoglycemia.

OPERATIONAL THRESHOLD It is defined as that concentration of plasma or BGL at

which clinicians consider intervention.

In Healthy term infants• < 24hrs of age- 30 to 35 mg/dl is acceptable at once.• > 24 hrs and infant with abnormal signs and symptoms-

threshold is increased to 45 to 50 mg/dl.

Asymptomatic infants with risk factors –threshold is 36mg/dl.

For any baby – if BGL is <20- 25 mg/dl, iv glucose needed.

ETIOLOGY Hyperinsulinemic hypoglycaemia: is the major cause of

recurrent/ persistent hypoglycaemia which is associated with

increased utilisation of blood glucose and inhibits

glycogenolysis & gluconeogenesis. Conditions are:-

• Infant of diabetic mother (IDM)

• ATP sensitive potassium channel defects

• Erythroblastosis

• Beckwith-Wiedemann syndrome

Infant of diabetic mum“Cherubic” facies

Picture- infant of diabetic mother ( macrosomia)

• Islet-cell dysmaturity

• Insulin-producing tumours (nesidioblastosis, islet-cell adenoma)

• Maternal drugs like beta-sympathomimetics (terbutaline)

• Abrupt cessation of high-glucose infusions

Picture- baby born with Beckwith-Wiedemann syndrome with a) Gigantism b)Macroglosia and c) Ear pits

Decreased production/stores

• Prematurity• Intrauterine growth retardation(IUGR)• Inadequate caloric intake• Delayed onset of feeding

Increased utilisation and/or decreased production

a) Perinatal Stress includes-• Sepsis • Shock• Asphyxia• Hypothermia • Post-resuscitation• Respiratory distress

b) Inborn error of metabolism includes

•Glycogen storage disease

•Fructose intolerance

•Galactosemia

•Maple syrup urine disease

•Propionic acidemia

•Methylmalonic acidemia

•Tyrosinemia

•Glutaric acidemia type 2

• Ethylmalonic adipic aciduria

c) Endocrine causes:

• Adrenal insufficiency

• Hypothalamic deficiency

• Congenital hypopituitarism

• Glucagon deficiency

• Epinephrine deficiency

Polycythemia

Maternal therapy with beta blockers like labetalol or

propanolol

Exchange transfusion

Clinical Manifestations•Patients are mostly asymptomatic or may present with some nonspecific

symptoms like:-

•Lethargy

•Irritability

•Hypotonia or limpness

•Sweating, tremors, jitteriness, abnormal cry (weak / high pitched)

•Hypothermia

•Poor feeding, vomiting

•Apnoea, irregular respiration, respiratory distress, cyanosis

•Tachycardia, CCF

•Seizures, coma

Screening in High Risk Infants •Indications for blood glucose screening are:-

•Low birth weight <2000 grams

•Preterm infants <35 weeks

•SGA and LGA

•Infants of diabetic mother

•Infants of Rh-hemolytic disease

• Infants born to mother of receiving beta-

sympathomimetics like terbutaline or oral hypoglycemic

• Infants with morphological IUGR

• Any sick neonate with birth asphyxia, sepsis, shock etc.

• Infants on total parenteral nutrition

Time Schedule For Screening Category of neonates Time Schedule

•At risk neonates 2,6,12,24,48 and 72 hrs

•Sick neonates Every 6-8 hrs (like sepsis, asphyxia, during shock)

•Stable VLBW neonates Initial 72 hrs every 6-8hrs on parenteral nutrition After 72 hrs once a day

DiagnosisSymptoms of hypoglycemia are nonspecific -

•Tremors, jitteriness or irritability

•Seizures, coma

•Lethargy and limpness

•Apnea

•Weak or high pitched cry

•Cyanosis

•Many neonates are asymptomatic

Screening of high risk infants.

Reagent strips with reflectance meter:- reagent strips are

of unproven reliability because

•Reagent strips measure whole blood glucose which is 15%

lower than plasma levels.

•Reagent strips provide false positive and false negative

results.

•A valid confirmatory laboratory glucose test is required

before to diagnose as hypoglycemia.

•One should not wait for lab glucose confirmation if blood

glucose is <45 mg/dl, treatment should be started

immediately.

Laboratory Diagnosis:-

•It is most accurate method to determine blood glucose level.

•It is done by glucose oxidase(calorimetric) method or glucose electrode method.

•It is should be done immediately to prevent glycolysis. Glucose level can fall @18 mg/dl/hr.

Critical Lab Test:- most hypoglycemia resolve in 2-3 days.

•If requirement of GIR is >8-10 mg/kg/min or hypoglycemia

persists >1 week suggests increased utilization of glucose

due to hyperinsulinism.

•Endocrine evaluation is necessary to evaluate

hyperinsulinism.

•Criteria of hyperinsulinism based on hyperinsulinemia

(insulin >2 μU/ml), hypoketonemia ( -β hydroxybutyrate <2

mmol/L) and hypofattyacidemia (FFA levels <1.5 mmol/L).

•Critical lab test includes-• Glucose • Insulin• Cortisol levels • Beta-hydroxybutyrate and free fatty acid levels

•If insulin level is normal then look for other causes of

persistent hypoglycemia such as inborn error of metabolism.

This includes-

• Growth hormone

• Adrenocorticotropic hormone(ACTH)

• Thyroxin (T4) and TSH

• Glucagon

• Plasma amino acids

• Urine ketones

• Urine-reducing substance

• Urine amino acids

• Urine organic acids

• Genetic testing for mutations like SUR1 and Kir6.2

Differential Diagnosis

If symptoms persist after glucose concentration is normal

then consider other etiologies such as:-

Sepsis

Metabolic abnormalities

•Hypocalcaemia

•Hyponatremia or Hypernatremia

•Hypomagnesaemia

•Pyridoxine deficiency

Adrenal insufficiency

Renal failure

Liver failure

Heart failure

CNS disease

Management Management of Asymptomatic Hypoglycemia-

Breastfeeding – DBM is the best option to prevent hypoglycemia. If infant is unable to suck EBM or Formula feed can be given.

If BGL is 20-45 mg/dl then

•Give trial of oral feeds (EBM or Formula feed) and repeat blood

glucose after 1hr

•If BGL is >45 mg/dl, 2 hourly feeds is ensured with 6 hourly

monitoring of BGL for 48 hrs target BGL is 50-120 mg/dl.

•If repeat BGL is <45 mg/dl IV dextrose is started and further

management is as for symptomatic hypoglycemia.

If BGL is <20 mg/dl then

• Start IV dextrose @6 mg/kg/min and subsequently

managed as for symptomatic hypoglycemia.

Management of Symptomatic Hypoglycemia:-

•All symptomatic infants should be treated with IV fluids.

•Indication of IV therapy- 1. Inability to tolerate oral feeding2. Symptomatic hypoglycemia3. Oral feeding do not maintain normal BGL4. BGL is <20 mg/dl

Infants with symptomatic hypoglycemia including seizures should given a bolus of 10% dextrose @2 ml/ kg and followed by continuous glucose infusion @6-8 mg/kg/min.

BGL should be checked after 30-60 min and then every 6 hourly until BGL is >50 mg/dl.

If BGL remains <45 mg/dl despite bolus and glucose infusion, increase GIR @2 mg/kg/min every 15-30 min until a maximum of 12mg/kg/min.

•GIR is calculated by following formula-

GIR(mg/kg/min) = % dextrose x ml/kg/day 144

•After 24hrs of IV dextrose 1 or 2 consecutive BGL are >50 mg/dl, infusion can be tapered @2 mg/kg/min every 6 hrly with BGL monitoring. It has to be accompanied by concomitant increase in oral feeds.

•Once the rate of 4mg/kg/min of infusion is achieved and oral intake is adequate with BGL >50 mg/dl, infusion can be stopped.

•Central venous line is needed if GIR requirement is >12

mg/kg/min due to risk of thrombophlebitis.

•Do not stop glucose infusion abruptly this causes rebound

hypoglycemia.

Fig. Showing Interconversion of glucose infusion units

Resistant /Recurrent Hypoglycemia

•It is condition in which infant is fails to maintain normal BGL

despite giving GIR of 12 mg/kg/min or when stabilization is

not achieved by 7 days of therapy.

•Besides increasing GIR certain drugs can be used in this

condition. Before starting these drugs send the samples

included in crirtical lab test.

•Drugs that used are following-

• Hydrocortisone @5mg/kg/day in 2 divided doses IV or

PO for 24-48 hours. Hydrocortisone reduces peripheral

glucose utilization, increases gluconeogenesis and

increases the effect of glucagon.

• Diazoxide @5-8 mg/kg/day in divided doses of 8-12

hourly. It inhibits the insulin release by acting as a ATP-

sensitive potassium channel agonist in normal

pancreatic beta-cells. It takes 5 days for a positive effect.

• Octreotide @5-20 mcg/kg/day IV or SC divided every 6-8

hourly. A long acting somatostatin that inhibits insulin

secretion.

• Glucagon @0.025-0.2 mg/kg IM, SC or IV max dose 1 mg is

rarely used. It acts by enhancing gluconeogenesis,

mobilizing hepatic glycogen stores and promoting

ketogenesis. Adverse effects are vomiting, diarrhea and

hypokalemia.

Follow Up & OutcomeOutcome of hypoglycemia depends on

•Duration of hypoglycemia

•Cerebral utilization of glucose

•Cerebral blood flow

• Degree of hypoglycemia

Some have no long term sequelae.

Symptomatic / severe / persistent hypoglycaemia may results in,• Abnormal neurointellectual development

• Cerebral palsy

• Epilepsy

• Cognitive impairment

• Visual problems

• Developmental & behavioural disorders

These infants should be assessed at 1 month for

vision/eye evaluation and at 3,6,9,12 and 18 month for

growth, neurodevelopment, vision and hearing loss.

Vision can be assessed by Teller equity card and hearing

assessment by BERA.

MRI at 4-6 weeks provides a good estimate to hypoglycemic

injury. MRI exhibit a typical pattern of CNS injury in the

pareito-occipital cortex and subcortical white matter.

THANK YOU