Neonatal Hypoglycemia

HYPOGLYCEMIA IN NEWBORN

Dr.David MendezMiami Childrens HospitalKidz Medical Services

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.

• New born – glycogenolysis, gluconeogenesis and exogenous nutrients.

DEFINITION

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.

ETIOLOGY

• Fetal or Neonatal Hyperinsulinism – ↑utilization of glucose.

Decreased production or store

Increased utilization and/or decreased production

Hypoglycemia of the newborn

Fetal or Neonatal Hyperinsulinism – ↑utilization 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).

Hypoglycemia of the newborn

Insulin producing tumors(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

Hypoglycemia of the newborn

Decreased production or store:

Prematurity

IUGR (15% in SGA)

Inadequate calorie intake

Delayed onset of feeding

Hypoglycemia of the newborn

Increased utilisation or decreased production:

Perinatal stress

Sepsis/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

Hypoglycemia of the newborn

Endocrine deficiency

Adrenal insufficiency

Hypothalamic deficiency

Hypopituitarism

(neonatal emergencies such as apnea, cyanosis, or severe hypoglycemia with or without seizures, hyperbilirubinemia, and micropenis. )

Glucagon def

Epn deficiency

Defects in amino acid metabolism

MSUD,propionic acidemia,MMA,tyrosinemia

Hypoglycemia of the newborn

• Polycythemia

-higher glucose utilization by increased mass of RBC

Maternal therapy with beta blockers

-Prevention of symp stimulation of glycogenolysis &epinephrine induced increase in FFA

DIAGNOSIS• SYMPTOMS

Tremors,jitteriness,irritability,seizures,lethargy, poor feeding,vomiting ,limpness,weak or high pitched cry ,cyanosis

ASYMPTOMATIC.

• MEASURMENT OF BLOOD GLUCOSE

glucometer- 15% lower than plasma levels

Lab diagnosis-sample obtained and analyzed promptly (18mg/dl/hr)

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

Routine screening in babies with risk factors

• 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

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

• Early introduction of breast feeds

o maintain stable BG levels without rebound HG

o keep ketone levels high---alternate fuel during 1st few days while baby adapts to DBF

o enhances gluconeogenesis

• IV therapy

Indications –

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

144

For 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 hr

Monitoring 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/diazoxide

Further 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

IDM

• <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

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

• Glucagon

Metabolic 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!

Neonatal Hypoglycaemia

Dr Varsha Atul Shah

Dept of Neonatal and Developmental Medicine

Singapore General Hospital

Extremes of Birth Weight

Neonatal Hypoglycaemia

Prematurity

Definition• Controversial

• Operational threshold• Pragmatic approach• i.e. blood glucose level at which clinical

intervention should be considered• Indication for action but not diagnostic of disease

• Symptomatic: < 45mg/dl (2.5mmol/L)• Asymptomatic & at-risk: < 36mg/dl (2.0mmol/L)

• Significant neonatal hypoglycaemia (Whipple’s triad)• Clinical manifestations• Coincident low plasma glucose level (laboratory)• Clinical signs resolve within mins - hrs of

establishing normoglycaemia

• Therapeutic objective• Raise plasma glucose level > 45mg/dl (2.5mmol/L)

• Term breastfed infants• Can utilise ketones as source of energy in

absence of glucose during transient starvation• May tolerate low glucose levels better

Clinical Features• Non specific

• Apathy, lethargy, irritability• Hypotonia, limpness• Sweating, tremors, jitteriness, abnormal cry

(weak / high pitched)• Hypothermia• Poor feeding, vomiting• Apnoea, irregular respiration, respiratory distress,

cyanosis• Tachycardia, CCF• Seizures, coma

• Asymptomatic

Aetiology

• utilisation of glucose: hyperinsulinism(Hyperinsulinism: inhibit glycogenolysis &

gluconeogenesis)• Infant of diabetic mother (IDM)• Erythroblastosis• Beckwith-Wiedemann syndrome• Islet-cell hyperplasia / hyperfunction• Insulin-producing tumours (nesidioblastosis, islet-cell

adenoma)• Maternal drugs (salbutamol, chlorpropamide)• Abrupt cessation of high-glucose infusions

Infant of diabetic mum

“Cherubic” facies

Beckwith-Wiedemann Syndrome

Macrosomia, macroglossia, omphalocele, hypoglycaemia, microcephaly

• production/stores• Prematurity• Intrauterine growth retardation• Inadequate caloric intake

IUGR

Premature

• utilisation and/or production or others• Stress

• Sepsis ( utilisation)• Shock• Asphyxia ( stores)• Hypothermia ( utilisation)

• Polycythaemia ( utilisation by red cell mass)

• Exchange transfusion• Inborn errors of metabolism

• Defect in carbohydrate metabolism

• Glycogen storage disease, fructose intolerance, galactosemia

• Defect in amino acid metabolism

• Maple syrup urine disease, propionic acidemia, etc

• Endocrine causes• Adrenal insufficiency, hypothalamic deficiency,

congenital hypopituitarism, glucagon deficiency, epinephrine deficiency

Management

• Prevention• Antenatal & intrapartum care

• e.g. control of maternal diabetes, causes of prematurity & IUGR

• Avoid environmental stress e.g. cold

• Early feeding / IV dextrose infusion

• Anticipation• Screening

1. At-risk babies

a. Maternal

e.g. drugs, intrapartum glucose, diabetes, etc

b. Neonatal

e.g. asphyxia / perinatal stress, premature, SGA / LGA, low birth weight, sepsis, shock, polycythaemia, etc

2. Those with symptoms

Non specific; high index of suspicion

• Diagnosis• Screening using glucose reagent strips

• Within 2 - 3 hrs after birth & before feeding (2 - 4 hrly) for 24 - 48 hrs & whenever symptomatic

• Confirmatory laboratory diagnosis important• Do not delay treatment while waiting for result• Analysed promptly to avoid falsely low value due

to glycolysis

• Treatment• Aim to maintain plasma glucose > 45mg/dl

(2.5mmol/L)

• IV dextrose• Mini bolus Dex 10% (2ml/kg) followed by infusion• Central line required for high dextrose

concentrations (> Dex 10%)• Continued close plasma glucose monitoring to

titrate infusion• Avoid abruptly decreasing dextrose infusion

(rebound hypoglycaemia)

• Adjunct therapy• Considered if persistent hypoglycaemia despite

glucose infusion > 10-12mg/kg/min

• Glucagon: stimulates glycogenolysis (adequate glycogen stores) (AGA/LGA)

• Hydrocortisone: peripheral glucose utilisation, gluconeogenesis, glucagon effects (prem/SGA)

• Rarely:• Diazoxide: inhibits insulin secretion

• Somatostatin: inhibits insulin & growth hormone release

• Subtotal pancreatectomy: decreases insulin release (insulin-secreting tumours)

• Most hypoglycaemia resolve in 2 - 3 dys

• Persistent / recurrent hypoglycaemia for > 1 week may require evaluation for other causes

• e.g. insulin, cortisol, other endocrine & IEM studies during period of hypoglycaemia

• During a period of hypoglycaemia, a normal infant’s blood insulin level should be low or absent. If it is very high suggests hyperinsulinism. It inhibits braeking down of glyconen

Significance of Hypoglycaemia

• Neuronal cell injury, cerebral damage, long term neurologic sequelae

• No single value below which or duration beyond which brain injury definitely occurs

• ? Vulnerability of brain of infants of different gestational ages

• Prevention, prompt treatment important

Symmetric patchy hyperintensities in occipital white matter in brain of infant with transient neonatal hypoglycaemia

Kinnala Peds 1999

Boy with isolated hypoglycaemia: computed tomography at 6 days of age shows cortical and white matter low density that is most severe in the parietal and occipital lobes

T2 weighted axial MRI at 10 months of age shows parenchymal loss posteriorly with high signal in the white matter of the parietal and occipital lobes (arrows). Note thin and atrophic gyri (arrowhead)

Traill, Arch Dis Child 1998

Boy with a variant of glycogen storage disease type 2b. Computed tomogram at 6 days of age shows low density in the cortex and white matter of the parietal and occipital lobes

T2 weighted axial magnetic resonance image at 7 years of age shows marked atrophy in the parietal and occipital cortex and underlying cerebral white matter

Traill, Arch Dis Child 1998

Outcome

• Varied

• Some have no long term sequelae

• Symptomatic / severe / persistent hypoglycaemia• Abnormal neurointellectual development

• Cerebral palsy• Epilepsy• Cognitive impairment• Visual problems• Developmental & behavioural disorders

Long Term Management

• Neurodevelopmental follow up to identify sequelae of neuroglycopenia

• Identify growth deficits