Hypoglycemia is one of the most common metabolic problems seen in newborn specially in sick neonate.

There is no universal definition for hypoglycemia.

Various investigators have empirically recommended different blood lucose levels (BGLs) that should be maintained in neonatal period to prevent injury to the developing brain.

The “normal” range of blood glucose is variable and depends upon factors like birth

weight, gestational age, body stores, feeding status, availability of energy sources as well as the presence or absence of disease

Further, there is no concrete evidence to show the causation of adverse long-term outcomes by a particular level or duration of hypoglycemia

Hence, a consensus has been to evolve an “operational threshold.”

Defined as that concentration of plasma or whole blood glucose at which clinicians should consider intervention.

Operational threshold has been defined as BGL of less than 40 mg/dL (plasma glucose level less than 45 mg/dL).

WHO defines hypoglycemia as BGL of less than 45 mg/dL.

Overall Incidence = 1- 5/1000 live births◦ Normal newborns – 10% if feeding is

delayed for 3-6 hours after birth ◦ At-Risk Infants – 30%

LGA – 8% Preterm – 15% SGA – 15% IDM – 20%

Glucose concentration is about 70% of maternal value

Enzymes for gluconeogenesis, presented by 3rd month of gestation.

Insulin starts production by 12 Wks and increases third trimester and fetal glycogen deposits begin ninth week and increases by third trimester

Glucagon starts production by15 weeks of gestation

Capable of using alternate substrate as ketone bodies and activate own glucose production

Newborn has two fold greater basal fasting than adults

Gluconeogenesis complements Glycogenolysis Increase Catecholamine levels (decrease temp

and loss of placenta) , + glycogenolysis Falling glucose causes surge in fetal cortisol Surge Glucagon and decrease in plasma insulin Lipolysis: FFA and Ketones Sparing glucose

utilization in heart, liver, muscle and brain (k), producing NADH for Gluconeogenesis.

Brain Glucose uptake is insulin independent, metabolism supported in part by oxidation ketones and lactate.

Glucose is the primary fuel for the brain.

The brain needs a steady supply of glucose to function normally.

Glucose is the fetus’s only source of carbohydrate.

Karlsen, 2006

“Compared with adults, infants have a higher brain to body weight ratio, resulting in higher glucose demand in relation to glucose production capacity”.

“Cerebral glucose utilization accounts for 90% of the neonate’s glucose consumption”.

Fetal plasma glucose is 60 – 80% of the maternal glucose level.

The fetus stores glucose in the form of glycogen (liver, heart, lung, and skeletal muscle).

Most of the glycogen is made and stored in the last month of the 3rd trimester.

The fetus has limited ability to convert glycogen to glucose and must rely upon placental transfer of glucose to meet energy needs.

When the infant is born, the cord is cut and so is the major supply of glucose!

The transition from fetus to newborn creates a significant energy drain on the newborn.

The newborn is now required to meet increased metabolic demands while changing the energy source from a placenta-supplied source to an external food source.

1 Low birth weight infants (<2000 grams)

2 Preterm infants (<weeks) 3 Small for gestational age infants

(SGA) : birth weight <10th percentile 4 Infant of diabetic mothers (IDM) 5 Large for gestational age (LGA)

infants: birth weight >90th percentile* 6 Infants with Rh-hemolytic disease

Infants born to mothers receiving therapy with terbutaline/propranolol/lebatolol/oral hypoglycemic agents

8 Infants with morphological IUGR 9 Any sick neonate such as those with

perinatal asphyxia, polycythemia, sepsis, shock etc

10 Infants on total parenteral nutrition

Secondary to Increased utilization of glucose

Inadequate supply of glucose

Combination of two

Karlsen, 2006

The most common cause is neonatal hyperinsulinemia-

Self limiting hyperinsulinemia- IDM Rhesus hemolytic disease PNA IUGR Antenatal administration of Thiazide Diuretics Iatrogenic Beckwith-Wiedemann Syndrome Congenital Hyperinsulinemic hypoglycemia

Three possible mechanism may cause failure of glucose production-

Reduced availability of gluconeogenic precursor-limited availability of glycogen.i.e.Preterm,IUGR,HIE,Inadequate substrate intake

Reduced activity of enzyme-sepsis,CHD,Cold injury,Preterm

Impaired counter-regulatory hormone- Preterm,IUGR,Maternal medication with b-

blocker

Glucose crosses the placenta Insulin does not cross the placenta Results – fetus produces own insulin

in the presence of elevated glucose from the mother

Excessive formation of oxygen radicals that damage the mitochondria

This increase in oxidative stress results disrupts vascularization of the developing tissues.

Hyperglycemia alters the expression of regulating genes leading to altered cellular mitosis and the normal timing of cell death. Excessive cell death results in fetal anomalies.

Caudal regression syndrome Hydronephrosis Renal agenesis Micropenis Cystic kidneys Intestinal atresias

Anencephaly Spina bifida Caudal dysplasia CNS damage as a result of

◦ Birth trauma (macrosomia)◦ Glucose and electrolyte abnormalities◦ Perinatal asphyxia

RDS CHD

◦ VSD◦ Asymmetric septal hypertrophy◦ Thickened myocardium◦ Transposition of the greater vessels

Polycythemia and vascular sludging

Transient Persistent

Insufficient calorie intake or delayed onset of feeding

LGA,SGA,IUGR Infants Infant of gestational or IDM Postmature ,Premature Infant Infection ,Sepsis shock Respiratory distress Perinatal stress Asphyxia/HIE Hypothermia/Hyperthermia

Polycythemia Erythroblastosis Foetalis

Defined as hypoglycaemia lasting for more than 7 days or infant who require higher amount of glucose(>10-12mg/kg/min) to maintain normal glucose level for over a week.

Causes – Hyperinsulinism –Congenital,B Cell

Adenoma,Syndrome(BW,Soto) Endocrine Disorder-GH Def,Cong

Hypopituitarism Inborn Error of metabolism-

Galactosemia,GSD,Fatty Acid oxidation defect,Disorder of amino acid metabolism

At risk group Presentation No. of Patient

Preterm Low substrateImmature hormoneFluid restrictionFeeding difficultyPoor Temp Control

IUGR Low substrateImmature hormoneFluid restrictionFeeding difficultyPoor Temp Control

IDM Hyperinsulinism

At risk group Presentation No. of Patient

Perinatal Asphyxia Low substrateExhausted Stress ResponseEnzyme DysfunctionFluid restrictionFeeding difficultyHyperinsulinism

Septicemia Exhausted Stress ResponseEnzyme DysfunctionFluid restrictionFeeding difficulty

Inborn error of Metabolism Defect of enzyme of Glycogenesis,Glycogenolysis,Fatty acid oxidation

Schedule of blood glucose monitoring

Category of infants Time schedule

SAt risk neonates 2, 6, 12, 24, 48, and 72 hrs

ex distribution:Sick infants (Infants with sepsis, asphyxia, shock during active phase of illness. Once the underlying condition is under control, frequency of screening can be reduced or

Every 6-8 hrs (individualize as needed)

Stable VLBW infants on parenteral nutrition

Initial 72 h: every 6 to 8 hrs After 72 hr: once a day

Clinical signs associated with hypoglycemia

Asymptomatic

Symptomatic: A smaller proportion of infants with hypoglycemia can be symptomatic. Clinical signs of hypoglycemia are variable and may include stupor, jitteriness, tremors, apathy, episodes of cyanosis

Cont.. convulsions, intermittent apneic spells

or tachypnea, weak and high pitched cry, limpness and lethargy, difficulty in feeding, and eye rolling.

Episodes of sweating, sudden pallor, hypothermia and cardiac arrest have also been reported.

Evaluation HistoryDoes the mother has any risk factor-

IDM,Preeclampsia, receiving I/V glucose during delivery or on oral terbutaline,oral hypoglycemic drug

If infant at risk for hypoglycemia-Prematurity,hypoxia/Asphyxia,hypothermia,Illness(respiratory distress,sepsis)

How much glucose is pt receivingIs there any symptoms of hypoglycemia,poor

feeding ,lethargy,apnea,jitteriness,seizureH/o consanguinity

Physical examinationIrritability,LethargyTachypneaCyanosisEye rollingWeak or high pitched cryExaggerated moro reflex

Features of underlying causeSigns of sepsis or shockIDM-

Macrosomic,large,plump,puffy,plethoric,Congenital malformation(GIT,Heart ,Renal, CNS Anomaly)

Hypopituitarism-Midline defect and micropenisGalactosaemia,Intra-uterine infection-CatarractBeckwith-Wiedemann Syndrome- Facial

dysmorphism ,Liver may be enlarged

CONT..Congenital Adrenal Hyperplasia-Ambiguous

genitaliaMaple Syrup Urine Disease-Smell of urine Anthropometry-LGA/SGA

InvestigationTransient Hypoglycemia:S.Glucose levelCBC to rule out sepsis & PolycythemiaS. electrolytePersistent Hypoglycemia:Aim is to

determine hyperinsulinemiaInitial study: S.Glucose and insulinS.KetoneS.LactateS.Ammonia

Other tests:S.PHCortisol & ACTH(Adrenal insufficiency)Growth hormone levelT4 &TSHUrinary Ketone and reducing substances or

amino acid and organic acid

MRI Changes

hyperintense lesions in the IC and CR, with reduced ADC values. B, Follow-up DWI obtained 4 days after symptom improvement shows that the hyperintense lesions have disappeared, with normalization of ADC values.

ManagementHypoglycemia(Blood sugar <45mg/dl)

Symptomatic Asymptomatic

Figure 1: Algorithm for management of neonatal hypoglycemia (Asymptomatic)4,5

ASYMPTOMATIC

25-45mg/dl <25mg/dl

Trial oral feeding

Monitor blood sugar after 30 to 60

mins

<45mg/dl

>45mg/dl

Follow symptomatic hypoglycemia

Monitor blood glucose 6-8 hrly

Stop after 48 hrs

Follow symptomatic hypoglycemia

Figure 2: Algorithm for management of neonatal hypoglycemia (Symptomatic)Symptomatic Hypoglycemia

Bolus of 2ml/kg 10% dextrose

I/V Glucose infusion@6mg/kg/min,monitor 30-60min interval till euglycaemic& then 6 hrly

Blood sugar>45mg/dl Blood

sugar<45mg/dl

Increase glucose infusion rate@2mg/kg/min upto 12mg/kg/min

Refer to specialist center

Stable for 24 hrs on i/v fluid

Weaning at 2 mg/kg/min every 6 hrs,monitor 6 hrly,increase oral

feedStop I/V Fluid when rate is 4mg/kg/min

Practical pointsUseful formulae for Calculating GIR

(Glucose Infusion Rate):(a) Infusion rate (mg/kg/min) = [ IV

rate(ml/kg/day)x % of dextrose ] / 144

(b) GIR (mg/kg/min) = % of dextrose being infused x rate (mL/hr)/ body weight (in kg) x 6

(c) Infusion rate = Fluid rate (mL/kg/day) x 0.007 x

% of dextrose infused (mg/kg/min)

Cont..When IV bolus glucose is indicated?Symptomatic hypoglycemiaBlood glucose <1.4 mmol/L  

Indication of IV fluid in hypoglycaemia:Symptomatic Blood glucose < 1.7 mmol/L Inability to tolerate oral feeding ( vomiting)Persistent hypoglycaemia despite adequate fluid

& glucose management

Resistant Hypoglycemia I

If hypoglycemia persist despite high glucose delivery rate than drug should be started-

Hydrocortisone 5 mg/kg/day IV or PO in two divided doses for 24 to 48 hrs

Diazoxide can be given orally 10-25 mg/kg/day in three divided doses

Octreotide (synthetic somatostatin in dose of 2-10 μg/kg/day subcutaneously two to three times a day.

Glucagon

Specific TreatmentCongenital HypopituitarismMetabolic Defect-GSD,Galactosemia

OutcomeThe outcome of hypoglycemia is determined by

factors like, duration, degree of hypoglycemia, rate of cerebral blood flow, cerebral utilization of glucose, and also co-morbidities.

It is unlikely that brief self limiting episodes are of neurological significance.

Adverse neurological signs have been associated with longterm outcome.

Special attention should be paid to neuro-developmental outcome, overall IQ, reading ability, arithmetic proficiency and motor performance.

PreventionIncrease awareness of conditions that

predispose an infant to hypoglycemiaEarly screening of at-risk infantsEarly and frequent feedingsMaintain temperature

Thank You