+

Dr. Abhishek Goyal

NEONATAL HYPOGLYCEMIA

2+INTRODUCTION Common metabolic problem Blood glucose in newborns are generally lower than older children

& adult Fetal glucose level maintained at 2/3 of maternal B.glucose by

transplacental route Glucose level fall in Ist 1-2 hrs,lowest value at age of 3 hrs,

increase and stabilise by 4 hrs. preterm and SGA may be at highest risk up to 36 h (range 0.8 to

34.2 h) There is no single value below which brain injury definitely occur.

3+DEFINITION

The operational threshold for hypoglycemia is defined as that concentration of plasma or whole blood glucose at which clinicians should consider intervention.

it do not define normal or abnormal

It is <45 mg % regardless of gestational age and whether or not symptoms are present

Whipple’s triad: low glucose level documented by accurate lab method Signs and symptoms of hypoglycemia Resolution of signs and symptoms on restoration of blood

glucose levels.

4+MECHANISM

Clinically significant NH is the result of an imbalance between glucose supply and other fuels such as ketone bodies, which are released from fat.

NH caused by a lower glucose threshold for suppression of insulin secretion

Decreased expression of enzymes in pathways of hepatic glycogenolysis, gluconeogenesis,or ketogenesis.

5+EFFECT OF HYPOGLYCEMIA

6+ETIOLOGY Delay in feeding Low birth weight infants specially<2000 grams Preterm infants (35 weeks) Small for gestational age infants (SGA) : birth weight

<10th percentile Infant of diabetic mothers (IDM) Large for gestational age (LGA) infants: birth weight >90th

percentile Infants with Rh-hemolytic disease ,erythroblastosis

7+ Infants born to mothers receiving therapy with

terbutaline/propranolol/labetalol/oral hypoglycemic agents Infants with morphological IUGR. Any sick neonate such as those with perinatal asphyxia,

polycythemia, sepsis, shock ,etc., when they are in active phase of illness.

Infant on TPN Exchange transfusion

Heparinized blood with low glucose level

CPD blood (relatively hyperglycemic---reactive hypoglycemia

Routine screening is recommended in above mentioned conditions.

8+SCHEDULE FOR SCREENING

At risk neonates : 2, 6, 12, 24, 48, and 72 hrs Sick infants : Every 6-8 hrs (individualize as

needed) TPN : Initial 72 h: every 6 to 8

hrs After 72 hr: once a day After Exchange : 2 hrs after infusing CPD blood

Infants exhibiting signs compatible with hypoglycemia at any time also need to be investigated.

9+PITFALL IN GLUCOSE ESTIMATION 1. glucose reagent strips

2. Laboratory diagnosis

3. continuous monitoring capillary sugar value is 10% to 15% lesser than that of

plasma value Arterial samples have slightly higher value compared to

venous or capillary the BGL can fall by 14 to 18 mg/dL per hour in samples

that await analysis.

This problem can be avoided by transporting the blood in tubes that contain a glycolytic inhibitor such as fluoride."

10+CLINICAL FEATURE1. ASYMPTOMATIC.

2. SYMPTOMATIC Tremors, jitteriness ,irritability,seizures, lethargy, poor

feeding,vomiting ,limpness,weak or high pitched cry ,cyanosis Episodes of sweating, sudden pallor, hypothermia and cardiac

arrest have also been reported.

CLINICALCONFIRMATION-whipples triad

11+MANAGEMENTInfants With Asymptomatic Hypoglycemia

1. If any time Blood sugar 20-45 mg/dL

Trial of oral feeds (expressed breast milk or formula) and repeat blood test after 1 hour.

a. Repeat BGL is >45 mg/dL, two hourly feeds is ensured 6 hourly monitoring of BGL for 48 hrs. the target blood glucose value is 50 to 120 mg/dL.

b.Repeat BGL is <45 mg/dL IV Dextrose is started at 6 mg/kg/min of glucose

2. If any time Blood sugar levels <20 mg/dL

IV Dextrose is started at 6 mg/kg/min of glucose

12+Infants With Symptomatic Hypoglycemia

Symptomatic hypoglycemia Bolus 2 ml/kg

10% dextroseIV glucose infusion @ 6 mg/kg/minMonitor hourly till euglycemic and

then 6 hrly

Blood sugar >50 mg/dL

Stable for 24 hours on IV fluids;2 values of blood sugar >50

mg/dL

Weaning at 2 mg/kg/min every6 hrs;

↑ oral feeds;Monitoring to continue 6 hrly

Stop IV fluids whenthe rate is 4 mg/kg/minand the infant is stable

Stop monitoring when 2values are more than 50 on

full oral feeds

Blood sugar <50 mg/dL

Increase glucose @ 2mg/kg/min tilleuglycemia

Increase till the glucoseinfusion rate is >12

mg/kg/min

Resistant hypoglycemia

HydrocortisoneDiazoxide (not in SGA)Glucagon (not in SGA)

Octreotide

13+ glucose infusion preferably using an infusion pump and without any interruption.

Do not stop glucose infusion abruptly as severe rebound hypoglycemia may occur.

Avoid using more than 12.5% dextrose infusion through a peripheral vein due to the risk of thrombophlebitis.

If there is persistent hypoglycemia, check the intravenous line for functioning. Also recheck the intravenous fluid preparation and infusion rate.

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

14+Resistant/recurrent Hypoglycemia when infant fails to maintain normal

BGL despite a GIR of 12 mg/kg/min when stabilization is not achieved by 7

days of therapy

15+Causes of resistant hypoglycemia

Congenital hypopitutarism Adrenal insufficiency Hyperinsulinemic states Galactosemia Glycogen storage disorders Maple syrup urine disease Mitochondrial disorders Fatty acid oxidation defect

+ 16

Investigation for resistant hypoglycemiaCritical lab sample Serum insulin levels Serum cortisol levels Free fatty acid levels and

Beta hydroxy butyrate

Other sample(if critical sample are normal) Growth hormone levels ACTH Thyroid profile Blood ammonia Blood lactate levels Urine ketones and reducing

substances Urine and sugar

aminoacidogram Galactose 1 phosphate uridyl

transferase levels Genetic testing

17+Hydrocortisone 10mg/kg/day in 2 div doses MOA-decrease peripheral glucose utilisation, increase

gluconeogenesis,increase effects of glucagon Rapidly tapered off in few days Before administration of HC ,obtain blood samples for insulin

and cortisol levels

18+

Glucagon Mobilising hepatic glycogen stores Infants with good glycogen stores Not in preterms and malnourished 0.025-0.3 mg/kg IM

Diazoxide (2-5mg/kg q8h PO) – in persistent hyperinsulinemia Epinephrine Subtotal pancreatectomy

19+ADDITIONAL TESTS:

Endocrine Evaluation Insulin GH Cortisol/ACTH T4,TSH GlucagonMetabolic work up ABG/Blood NH3/ lactate Plasma or urine amino acids Urine organic acids Urine ketones/Urine reducing substance

20+

Na /K-adrenal insufficiency MRI brain-hypothalamic/pituitary pathology CT abdomen-islet cell adenoma

Genetic testing – to look for mutations

21+ Samples to detect insulin levels should be drawn at the time of low BG

 Criteria for Diagnosing Hyperinsulinism Based on “Critical” Samples

1. Hyperinsulinemia (p.insulin >2 μU/mL) 2. Hypofattyacidemia (p. FFA<1.5 mmol/L) 3. Hypoketonemia (p. β-hydroxybutyrate: <2.0 mmol/L) 4. Inappropriate glycemic response to glucagon, 1 mg IV

(rise >40 mg/dL)

22+

Hypoglycemia

Urine non glucose red substance

Present absent

Galactosemia ketones

23+

ketones

high low(nonketotic HG)

gluconeogenic FA oxidation defect

defect or or

Organic acidemia Ketogenic defect

Hyperinsulinism

24+DIFFERENTIAL DIAGNOSIS:

SepsisCNS diseaseMetabolic

abnormalities(hypocalcemia,hyponatremia,hypernatremia,hypomagnesemia,pyridoxine deficiency)

Adrenal insufficiencyRenal failureLiver failureHeart failure

25+

THANK YOU!

26+MANAGEMENT

The major long-term sequelae of severe, prolonged hypoglycemia are mental retardation, recurrent seizure activity, or both.

Permanent neurologic sequelae are present in 25–50% ofbabies with severe recurrent symptomatic hypoglycemia

These sequelae are more likely when alternative fuel sources are limited, as occurs with hyperinsulinemia

Anticipation and prevention –key to management of infants with risk factors for HG