1. NEONATAL HYPOGLYCAEMIA Dorothy Millar ST3

2. Learning Points  Symptomatic vs. asymptomatic  Babies at risk  Why its important  Management on postnatal wards  Rarer causes  Summary

3. Asymptomatic hypoglycaemia  Brief period of asymptomatic hypoglycaemia is universal in babies  Term babies mount a brisk response and can use alternative fuels (brown fat)  No evidence this episode is harmful in these babies

4. Symptomatic  Symptoms that suggest hypoglycaemia is likely to cause brain damage include  Apnoea  Seizures  Coma  Symptomatic hypoglycaemia in a term baby without risk factors is unusual and requires investigation  About 30% of babies with the above symptoms will have severe neurological abnormalities (severe LD, spastic quadriplegia)

5. Babies at risk  Low birthweight (<2.5kg)  Preterm (<36/40)  Macrosomic babies  Hypoxia  Infants of diabetic mothers  Polycythaemia  (Poor feeding)

6. Symptoms of hypoglycaemia  Jittery  Drowsiness, lethargy  Poor feeding  Hypothermia  Hypotonia  Cyanosis  Apnoeas  Seizures  Coma

7. Causes of hypoglycaemia  Poor feeding  Sepsis  Hypothermia  Transient  Polycythaemia  Hyperinsulinaemic hypoglycaemia  Syndromes  Metabolic disease

8. Management on postnates  Babies at risk:  Infants in a cold environment  Preterm <37 or post term ≥42 weeks  IUGR or LBW <2.5kg  Infants of diabetic mothers OR birthweight >4.5kg  Babies who require resus  Babies not tolerating feeds  Mum on Beta blockers  (Breast)feed early  Keep warm  Regular BM’s (not before 4hrs of age)  Pre-feed BM’s

9.  Sporadic  Neonatal hyperinsulinism  up to 50% with 5% persistent  Polycythaemia  Macroglossia  Macrosomia/ hemihypertrophy  Abnormal ear helix  Abdominal wall defects  umbilical hernia/ omphalocele)  Associated with Wilm’s tumour  6.5% so need regular screening Beckwith-Wiedemann syndrome

10. Endocrine causes  May be multiple or single endocrinopathy  Panhypopituitarism  Hypoglycaemia, prolonged jaundice, hyponatraemia, small genitalia  Congenital adrenal hyperplasia  Salt wasting (males), ambiguous genitalia (girls)  Hypothyroidism

11. Inborn errors of metabolism  Glycogen storage diseases  Type 1 – Von Gierke’s  Glucose 6 phosphatase deficiency  Galactosaemia  Medium chain acyl-CoA dehydrogenase deficiency (MCAD)  No tolerance of fasting (cannot use alternative fuels  Leads to hypoglycaemia - ?SIDS  Aminoacidopathies

12. Hyperinsulinaemic hypoglycaemia  Inappropriate secretion of insulin by pancreas  Insulin drives glucose into sensitive tissues (skeletal muscle, liver, adipose)  Inhibits glucose production (glycolysis and gluconeogenesis)  Suppresses fatty acid release and ketone synthesis  Therefore high risk of brain injury as brain deprived of both glucose and ketones

13. Causes of hyperinsulinism  Congenital  Secondary to risk factors (maternal DM, birth asphyxia, IUGR)  Associated with syndromes (BW)  Rare metabolic syndromes (eg congenital disorders of glycosylation)

14. Clinical features  Presents with severe hypoglycaemia in neonatal period  Refractory to feeds; infants need IV Dextrose in high concentration  Macrosomic due to fetal hyperinsulinism  This also causes HCOM and hepatomegaly  Those due to “risk factors” tend to be transient  However, IUGR + perinatal asphyxia can have a protracted course

15. Diagnosis  IV glucose dependence  Over 8mg/kg/min ( normal = 4-6mg/kg/min)  Glucose requirement = ml/h x % dextrose (mg/kg/min) 6 x weight (kg)

16. Diagnosis (cont.)  Inappropriate serum insulin and c-peptide levels for the glucose level  ie a normal insulin level at a low blood sugar is an inappropriate response  May also be a blunted counter-regulatory response  Low cortisol and glucagon levels

17. Acute Management  Priority is to maintain normoglycaemia  Higher threshold of hypoglycaemia (3.5 – 6mmol)  Require central access for >12.5% dextrose  Oral feeds with extra CHO (eg Maxijul) plus IV Dextrose  IM glucagon in emergency  However high doses causes paridoxical insulin release so also need IV dextrose

18. Long term management  Diazoxide  Blocks ATP channels to prevent depolarisation of β cell membrane  Causes fluid retention (esp in neonates)  Often used with chlorthiazide which has hyperglycaemic properties  Octreotide + frequent feeding  Long acting Somatostatin analogue  Inhibits release of insulin  Genetic analysis, 18F DOPA-PET scan, Surgery

19. Summary  Babies can be symptomatic or asymptomatic  Important to recognise babies at risk  Untreated can lead to brain injury and long term consequences  Values vary between centres but at NGH is <2.6 mmol/L  Different causes compared with older children  HH is rare but important to treat swiftly