1. Neonatal Hypoglycemia NICU Night Team Curriculum 1

2. Objectives Define neonatal hypoglycemia Know the causes of neonatal hypoglycemia Know signs and symptoms of hypoglycemia Understand treatment

3. Case 39 wk F born by NSVD to a 22 y/o G 1 P 0 mom with diet controlled GDM A 1. Mom’s blood sugars throughout the pregnancy ranged from 120-160. Maternal serologies were negative, pregnancy otherwise unremarkable. APGARS were 8 and 9 at 1 and 5 minutes, respectively. BW was 4,000 g.

4. Physical Examination VS: T 36.5 P 148 RR 80 BP 55/38 mmHg HC 34 cm (75%), Lt 50 cm (75%), BW 4,000 (>97%) GA: Well appearing F, NAD, no cyanosis HEENT: AF 2x2 cm, no cleft lip and palate Heart: RR, no murmur Lungs: Tachypneic breathing with even breath sounds throughout, no retractions, no flaring Abdomen: Soft ND, no hepatosplenomegaly Genitalia: Normal female genitalia Extremities: No deformities, MAEE

5. Labs 1 hour of life: Hematocrit 56% Dexi 30 mg% Serum glucose 34 mg%

6. What is your primary concern in this patient?

7. Neonatal Hypoglycemia Impaired glucose metabolism Serum blood glucose < 40 mg/dL OR Point of Care testing (accucheck, Dexi) <45

8. Why was a Dexi checked in this patient? She is at risk for developing hypoglycemia

9. Definition: A plasma glucose of less than 40 mg/dl Plasma glucose is higher than whole blood glucose by 15% Hypoglycemia

10. Fetal Glucose Metabolism Fetus does not produce glucoseFetus does not produce glucose Maternal glucose is the only source of fetal glucoseMaternal glucose is the only source of fetal glucose Baseline fetal blood glucose is 60-70% of maternal serum glucoseBaseline fetal blood glucose is 60-70% of maternal serum glucose Physiology

11. Glucose metabolism after birth Cessation of maternal glucose supply Blood glucose Nadir ( ~1-2 hrs after birth) Physiology

12. Glucose Metabolism After Birth Cessation of maternal glucose supply Surge in glucagon, catecholamine Decrease insulin Gluconeogenesis: Hepatic glycogen, amino acid, fatty acid metabolism Normal blood glucose

13. Etiology of neonatal hypoglycemia 1.Increased utilization (e.g.: hyperinsulinism) 2.Decreased production/stores 3.Increased utilization and/or decreased production

14. Increased Utilization Diabetic motherDiabetic mother Large for gestational age (LGA) infantLarge for gestational age (LGA) infant ErythroblastosisErythroblastosis Islet cells hyperplasiaIslet cells hyperplasia Beckwith-Wiedemann syndromeBeckwith-Wiedemann syndrome Insulin producing tumorsInsulin producing tumors Maternal tocolytic therapy with B-sympathomimetric agentsMaternal tocolytic therapy with B-sympathomimetric agents Malposition of umbilical artery catheterMalposition of umbilical artery catheter

15. Decreased Production/Stores PrematurityPrematurity Intrauterine growth retardation(IUGR)Intrauterine growth retardation(IUGR) Inadequate caloric intakeInadequate caloric intake Delayed onset of feedingDelayed onset of feeding

16. Increased utilization AND Decreased production Perinatal stress eg. shock, sepsis, asphyxiaPerinatal stress eg. shock, sepsis, asphyxia Enchange transfusionEnchange transfusion Defect in carbohydrate metabolism eg. glycogen storage diseaseDefect in carbohydrate metabolism eg. glycogen storage disease Endocrne deficiency eg. adrenal insufficiency, hypopituitarismEndocrne deficiency eg. adrenal insufficiency, hypopituitarism Defect in amino acid metabolismDefect in amino acid metabolism PolycythemiaPolycythemia Maternal therapy with B-blockerMaternal therapy with B-blocker

17. When do you screen? 1.Symptoms that could be due to hypoglycemia. 2.At risk infants.

18. What are signs and symptoms of hypoglycemia?

19. Signs and Symptoms of Hypoglycemia Symptoms are NON-SPECIFIC Jitteriness Apnea Irritability Grunting Lethargy Seizures

20. Who is at risk? Infants of diabetic mothersInfants of diabetic mothers Maternal use of B-adrenergic agonist/ antagonistMaternal use of B-adrenergic agonist/ antagonist IUGRIUGR LGALGA PretermPreterm PolycythemiaPolycythemia AsphyxiaAsphyxia Sick infantSick infant

21. When is the ideal time to screen high risk infants?

22. Screening Blood glucose or point of care testing (POC) should be done in high risk infants within the first 1 to 2 hours after birth

23. Back to our case: 1.Term LGA infant 2.IDM with poor blood glucose control 3.Tachypnea 4.Hypoglycemia

24. Why do you think she developed hypoglycemia? Hyperinsulinism

25. Pathophysiology : infants of diabetic mothers

26. Feeding? IV therapy? Medication? How do you treat this patient?

27. Management – Oral Feeds Can be used in asymptomatic infantsCan be used in asymptomatic infants Only formula (never administer glucose water!!)Only formula (never administer glucose water!!) Follow up blood glucose within 1 hour of feeding.Follow up blood glucose within 1 hour of feeding. If the glucose level doesn’t rise, a more aggressive therapy may be needed.If the glucose level doesn’t rise, a more aggressive therapy may be needed.

28. Management – IV therapy Indications: Inability to tolerate oral feedingInability to tolerate oral feeding Symptomatic infantSymptomatic infant Lack of response with oral feedsLack of response with oral feeds Glucose < 25 mg/dL, regardless of patient’s symptomsGlucose < 25 mg/dL, regardless of patient’s symptoms

29. Management – IV therapy Urgent treatment Bolus 2 ml/kg of D10WBolus 2 ml/kg of D10W Do not use 25% or 50% glucose !!Do not use 25% or 50% glucose !! Follow bolus with continuous dextrose fluidFollow bolus with continuous dextrose fluid

30. Continuing IV fluid Start infusion of glucose at a rate of 6-8 mg/kg/minStart infusion of glucose at a rate of 6-8 mg/kg/min Glucose infusion rate formula (GIR):Glucose infusion rate formula (GIR): GIR = %IV fluid x rate(ml/hr) 6 x BW(kg) 6 x BW(kg) Management – IV therapy

31. Re-check serum glucose 20-30 min after bolus and hourly until stableRe-check serum glucose 20-30 min after bolus and hourly until stable –If glucose is normal and stable, feeding may be continued and glucose infusion tapered –If glucose can’t be maintained > 50 mg/dL, increase GIR by 1-2 mg/kg/hr –If glucose can’t be maintained > 50 mg/dL, with a GIR 12 mg/kg/min, medication should be added.

32. Management – Medication Persistent hypoglycemia despite a GIR > 12 mg/kg/min. Persistent hypoglycemia despite a GIR > 12 mg/kg/min. Work up – Critical Labs:Work up – Critical Labs: –Serum cortisol, insulin, growth hormone when glucose is low and prior to treatment –DO NOT wait >5 minutes for labs prior to treating hypoglycemia MedicationMedication –Hydrocortisone –Glucagon –Diazoxide

33. Hydrocortisone Dose: 10 mg/kg/day IV q 12 hrsDose: 10 mg/kg/day IV q 12 hrs Indication: Hypoglycemia despite GIR > 12 mg/kg/minIndication: Hypoglycemia despite GIR > 12 mg/kg/min Send hormone level before starting hydrocortisone!!!Send hormone level before starting hydrocortisone!!!

34. Glucagon Dose: 0.025-0.3 mg/kg IM/IV (maximum 1 mg)Dose: 0.025-0.3 mg/kg IM/IV (maximum 1 mg) Should cause recovery of hypoglycemiaShould cause recovery of hypoglycemia May not work ifMay not work if –Reduced glycogen stores –Glycogen storage disease

35. Diazoxide Dose: 2-5 mg/kg/dose PO q 8 hrs.Dose: 2-5 mg/kg/dose PO q 8 hrs. Indication: Infants who have persistent hyperinsulinemia (e.g.. Nesidioblastosis)Indication: Infants who have persistent hyperinsulinemia (e.g.. Nesidioblastosis)

36. Remember, he was tachypneic Urgent treatment:D10W 2 mL/kg IV bolus followed by continuous IV fluid Back to our case: How would you treat our patient?

37. Board Question A term infant was born to a pre-ecclamptic mother. BW was 2,000 g (<10 th %). Physical exam was normal. Blood glucose at 2 hour of age was 30 mg/dL What is your next step in management? a. D10W bolus of 4 mL b. D10W continuous IV infusion at 6.5 ml/hr c. 20 mL of oral glucose water d. 20 mL of infant formula

38. Board Question A term infant was born to a pre-ecclamptic mother. BW was 2,000 g (<10 th %). Physical exam was normal. Blood glucose at 2 hour of age was 30 mg/dL What is your next step management? a. D10W bolus of 4 mL b. D10W continuous IV infusion at 6.5 ml/hr c. 20 mL of oral glucose water d. 20 mL of infant formula

39. Reference Wilker RE. Hypoglycemia and hyperglycemia. In: Cloherty JP, Eichenwald EC, Stark AR, eds. Manual of Neonatal care. 5 th ed. Lippincott Williams & Wilkins; Philadelphia; 2008: 540-549Wilker RE. Hypoglycemia and hyperglycemia. In: Cloherty JP, Eichenwald EC, Stark AR, eds. Manual of Neonatal care. 5 th ed. Lippincott Williams & Wilkins; Philadelphia; 2008: 540-549 Cornblath M, Ichord R. Hypoglycemia in the neonate. Semin Perinatol 2000;24:136-149Cornblath M, Ichord R. Hypoglycemia in the neonate. Semin Perinatol 2000;24:136-149 Sperling MA, Menon RK. Differential diagnosis and management of neonatal hypoglycemia. Pediatr Clin North Am 2004;51:703-723Sperling MA, Menon RK. Differential diagnosis and management of neonatal hypoglycemia. Pediatr Clin North Am 2004;51:703-723