1. HYPOGLYCEMIA AND HYPERGLYCEMIA Izaskun C. Ganao

2. Hypoglycemia  Almost all fetal glucose is derived from the maternal circulation  The severing of the umbilical cord abruptly interrupts the source of glucose  To maintain adequate glucose levels  Glycogenolysis of hepatic stores inducing gluconeogenesis  Feeding  During this transition, glucose levels fall in the first 1 to 2 hours and then increase and stabilize at 65 to 70 mg/dl by the age of 3 to 4 hours

3.  Incidence  16% of LGA  15% of SGA

4.  Definition of hypoglycemia: Operational Threshold  Indication for action; not diagnosis  Lower than therapeutic goal  Dependent on clinical state and age  Do not define normal or abnormal  Provide margin of safety

5.  Cornblath’s description of operational thersholds  Healthy term infant <24 hours of age – 30 to 35 mg/dl is acceptable; should be raised to 45 mg/dl after feeding >24 hours – 45-50mg/dl  Infant with abnormal signs of symptoms – 45 mg/dl  Asymptomatic infants with risk factors for low blood sugar – 36 mg/dl  For any baby, if glucose levels are 45mg/dl

6.  There is no single value by which brain injury definitely occurs  Normal asymptomatic babies may have a transient glucose level in the 30s that will increase spontaneously or with feeding  Goal  45 mg/dl in the 1 st day  >50 mg/dl after the 1 st day

7. Etiology 1. Hyperinsulinemic hypoglycemia  Infants of diabetic mothers  Congenital genetic hyperinsulnism  Secondary to other conditions: Birth asphyxia Developmental syndromes such as Beckwith-Wiedemann syndrome) Congenital disorders of glycosylation Erythroblastosis Maternal tocolytic therapy with beta-sympathomimetic agents (terbutaline) Malposition umbilical artery catheter used to infuse glucose in high concentration into the celiac and superior mesenteric arteries – stimulating insulin release from the pancreas Abrupt cessation of high glucose infusion After exchange transfusion with blood containing high glucose concentration Insulin-producing tumors

8. Etiology 2. LGA 3. Decreased production/stores  Prematurity  IUGR  Inadequate caloric intake  Delayed onset of feeding

9. Etiology 4. Increased utilization / decreased production a. Perinatal stress Sepsis Shock Asphyxia Hypthermia Respiratory disetress Postresuscitation

10. b. Defects in carbohydrate metabolism Glycogen storage disease Fructose intolerace Galactosemia c. Endocrine deficiency Adrenal insufficiency Hypothalamic deficiency Congenital hypopituitarism Glucagon deficiency Epinephrine deficiency

11. d. Defects in amino acid metabolism Maple syrup urine disease Propionic acidemia Methylmalonic acidemia Tyrosinemia Glutaric acidemia type II Ethylmalonic adipic aciduria e. Polycythemia - higher glucose utilization f. maternal therapy with beta-blockers

12. Diagnosis  Symptoms  Tremors, jitteriness, irritability  Seizures, coma  Lethargy, apathy, limpness  Poor feeding, vomiting  Apnea  Weak or high-pitched cry  Cyanosis  asymptomatic

13. Diagnosis  Screening  Done in infants with risk factors and with symptoms  30 to 60 minutes of life  IGDM  SGA  Erythroblastosis fetalis (hyperinsulinism)

14. Differential Diagnosis  Sepsis  CNS disease  Toxic exposure  Metabolic abnormalities (hypocalcemia, hypo or hypernatremia, hypomagnesemia, pyridoxine deficiency)  Adrenal insufficiency  Heart, renal, and liver failure

15. Management  Well infants at risk (IGDM)  Measure blood glucose levels and treat accordingly  Other asymptomatic infants at risk  HGT on the 1 st 1 to 2 HOL  Breastfeed or give formula ASAP then every 2 to 3 hours  20 to 25 mg/dl – IV glucose. Goal is to maintain the glucose >45 mg/dl in the 1 st 24 hours and >50 thereafter

16. Management  Feeding  Asymptomatic with hgt 30mg/dl Breastfeeding or formula Repeat hgt 1 hour after onset of feeding Glucose water not recommended

17. IV therapy  Indications  Inability to tolerate oral feeding  Symptoms  Oral feedings do not maintain normal glucose levels  Glucose levels less than 25mg/dl  Urgent treatment  200mg/dl of glucose over 1 minute, to be followed by continuing therapy Equivalent to 2ml/kg of dextrose 10% in water (D10W) IV

18. IV therapy  Continuing therapy Glucose infusion at 6 to 8 mg of glucose/kg/minute D10W at a rate of 86.4ml/kg/day or 3.6 ml/kg/hr gives 6 mg/kg/minute of glucose Glucose infusion rate (GIR) (GIR) in mg/kg/min= dextrose % concentration x ml/kg/day 144 e.g.: an infant receiving D10W at 80ml/kg/day GIR= 10 x 80 = 5.6 mg/kg/min. 144

19. IV therapy  Continuing therapy Repeat hgt after 20 to 30 minutes then hourly until stable to determine if IV therapy still needed Additional bolus infusions of 2mg/kg of D10W may be needed If glucose is stable and in acceptable range, continue feedings and taper infusions as permitted by glucose levels prior to feeding  May give D10W at maintenance rate  Infants with hyperinsulinism or IUGR – 12 to 15 mg of dextrose per kg per minute (often as 15% or 20% dextrose water)

20. IV therapy  May give hydrocortisone at 5mg/kg/day to reduce peripheral glucose utilization  Diazoxide – for persistently hyperinsulinemic infants  Octreotide – if diazoxide not effective  Glucagon – for mobilization of glucose (if the infant has good glycogen stores)  Imaging studies for pancreatic function

21. Hyperglycemia  Whole blood glucose level of >125mg/dl or plasma glucose level of >145mg/dl  Common in infants with LBW receiving parenteral glucose  Clinical problems  Hyperosmolarity  Osmotic diuresis if osmolarity >300 mOsm/L  Possible diabetes mellitus

22.  Etiology  Exogenous parenteral glucose  Drugs Steroids Caffeine Theophylline Phenytoin Diazoxide  ELBW infants  Lipid infusion

23.  Etiology  Sepsis – due to depressed insulin release, cytokines, endotoxin resulting in decreased glucose utilization  “stressed” premature infants  Hypoxia  Surgical procedures  Neonatal DM – usually SGA term infants, no gender predilection, with family hx of DM  Diabetes due to pancreatic lesions

24.  Etiology  Transient hyperglycemia associated with ingestion of hyperosmolar formula  Hepatic glucose production  Immature development of glucose transport proteins (GLUT-4)

25. Treatment  Hgt monitoring in premature infants and infants with abnormal symptoms  ELBW infants should start with a GIR of at least 4 to 6 mg/kg/min  Parenteral nutrition ASAP in LBW infants. Some amino acids promote insulin secretion  Feeding  Exogenous insulin therapy of glucose levels >250mg/dl  Oral sulfonylureas (long term therapy)

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