Neonatal Neonatal HypoglycaemiaHypoglycaemia

Dr Varsha Atul Shah

Dept of Neonatal and Developmental Medicine

Singapore General Hospital

Extremes of Extremes of Birth WeightBirth Weight

Neonatal Neonatal HypoglycaemiHypoglycaemiaa

PrematurityPrematurity

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

• 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

Management

• Anticipation– Screening

1. At-risk babiesa. Maternal

e.g. drugs, intrapartum glucose, diabetes, etcb. 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. insulininsulin, 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