HYPOGLYCEMIA IN

NEWBORNDr. Abhijeet Deshmukh

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.

New born – glycogenolysis, gluconeogenesis and exogenous nutrients.

INTRODUCTION

Defined as a blood glucose level of <40mg % 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.

DEFINITION

Fetal or Neonatal Hyperinsulinism – ↑utilisation of glucose.

Decreased production or store

Increased utilisation and/or decreased production

ETIOLOGY

Fetal or Neonatal Hyperinsulinism – ↑utilisation of glucose.

Babies born to Diabetic mothers(15-25 % GDM,25-50% DM)

LGA infants-16% Erythroblastosis Islet cell hyperplasia Beckwith-

weidemann(macrosomia,microcephaly,omphalocoele,macroglossia,visceromegaly).

Insulin producing tumours(islet cell adenoma).

Maternal therapy with tocolytics like terbutaline,ritodrine, OHA and diuretics (chlorothiazide)

Glucose infusion through UAC –high glucose into celiac,SMA—stimulate insulin from pancreas

Decreased production or store:

Prematurity IUGR (15% in SGA) Inadequate calorie intake Delayed onset of feeding

Increased utilisation or decreased production:

Perinatal stressSepsis/shock/asphyxia/respiratory

distress/hypothermia/post resuscitation.

Exchange transfusion Heparinised blood with low glucose level CPD blood (relatively hyperglycemic---

reactive hypoglcemia

Defects in carbohydrate metabolism Glycogen storage disease Fructose intolerance Galactosemia

Endocrine deficiencyAdrenal insufficiencyHypothalamic deficiencyHypopituitarism (neonatal emergencies such as apnea, cyanosis, or severe

hypoglycemia with or without seizures, hyperbilirubinemia, and micropenis. )

Glucagon defEpn deficiency

Defects in amino acid metabolism MSUD,propionic

acidemia,MMA,tyrosinemia

Polycythemia-higher glucose utilisation by increased mass of

RBC

Maternal therapy with beta blockers-Prevention of symp stimulation of glycogenolysis

&epinephrine induced increase in FFA

SYMPTOMSTremors,jitteriness,irritability,seizures,letharg

y, poor feeding,vomiting ,limpness,weak or high pitched cry ,cyanosis

ASYMPTOMATIC.

MEASURMENT OF BLOOD GLUCOSEglucometer- 15% lower than plasma levelsLab diagnosis-sample obtained and analyzed

promptly (18mg/dl/hr)

CLINICALCONFIRMATION-whipples triad

DIAGNOSIS

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

MANAGEMENT

Routine screening in babies with riskfacors SGA/Smaller of the discordant twin IDM/LGA Preterm <35 weeks On IVF/TPN Prolonged hypoxia

/hypothermia/polycythemia/septicemia/ suspected IEM

After exchange tranfusion Rh Hemolytic d/s Babies born to mothers on terbutaline/b-

blockers/OHA Symptomatic babies

Screening within 1 hr of birth IDM-0,1,3,6 ,12,18.24,48,72 hrs For 72hrs - risk babies ET-2 hrs after infusing CPD blood

Asymptomatic

25-40mg% <25mg%

Trial of feeds Parenteral

>40 <40

Continue oral feeds and monitor for 48 hrs

Early feeding with glucose water raises BG only transiently and asso with rebound hypoglycemia

Early introduction of breast feedso maintain stable BG levels without rebound HGo keep ketone levels high---alternate fuel during 1st

few days while baby adapts to DBFo enhances gluconeogenesis

IV therapyIndications – intolerance to oral feeds Symptomatic oral feeds not maintaining glucose levels BG level < 25mg/dl

o IV glucose through a peripheral line or UVC

o Urgent treatment- 2 ml/kg(200mg/kg) of 10% dextrose over 2-3 min.

o Severe distress – 2-4 ml/kg 25%D(1g/kg glucose) @ 1ml /kg/mt

For eg 2 kg infant-4-8 ml of 25% Dex in 2-4mt

o In asymptomatic baby with low BG levels initial push of conc sugar →→hyperinsulinism. Therfore, infusion 5-10 ml of 10% D at 1 ml/mt

Continuing therapy – based on Glucose Infusion Rate

GIR(mg/kg/min) = % dextrose x ml/kg/day 144For eg.86 ml/kg/day of 10% D--GIR 6-8[GIR of 8.33 = 80ml/kg/day of 15%D]

Monitor BG hourly till euglycemic and thereafter 6th hrly

If BG > 40mg%,Continue same and monitor

When 2 BG values >50 mg%,wean GIR by 2mg/kg/mt 6th hrly and start oral feeds

Stop infusion when baby is stable @4mg/kg/mt for 12 hrMonitoring stopped when 2 values on oral feeds >50mg

%

If BG < 40 mg%

Repeat bolus & increase GIR by 2mg/kg/mt every 6 hr till euglycemic

If GIR >12 or HG not resolving by day 7

steroids/glucagon/diazoxideFurther investigations

Check blood glucose after 30 mts of every change in infusion rate

Monitoring of glucose levels--to ensure adequate correction of

hypoglycemia -To avoid hyperglycemia---diuresis---

dehydration

<2kg –parenteral therapy in the 1st hour of life

>2 kg- can be fed hourly, for 3 or 4 feeds ,and then 2 hrly

As interval increase ,vol ↑ If by 2 hrs ,despite feeding GRBS< 40 mg

%--parenteral therapy

IDM

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

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

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

Na /K-adrenal insufficiency MRI brain-hypothalamic/pituitary pathology CT abdomen-islet cell adenoma Genetic testing – to look for mutations

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)

Hypoglycemia

Urine non glucose red substance

Present absent

Galactosemia ketones

ketones high low(nonketotic HG) gluconeogenic FA oxidation defect defect or or Organic acidemia Ketogenic defect Hyperinsulinism

DIFFERENTIAL DIAGNOSIS:

Sepsis CNS disease Metabolic

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

Adrenal insufficiency Renal failure Liver failure Heart failure

THANK YOU!