Hypobilirubinemia baby.docx

Fetal Neonatal Metabolism For energy needs, the fetus depends on maternal transfer of: Glucose AA FFA Ketones Glycerol There is no fetal glucose production After cord clamping: Glucose decreases rapidly and then increases over 2-3 hours. During the 1st day birth 50% of baby’s endogenous glucose come...

Fetal Neonatal Metabolism For energy needs, the fetus depends on maternal transfer of: Glucose AA FFA Ketones Glycerol There is no fetal glucose production After cord clamping: Glucose decreases rapidly and then increases over 2-3 hours. During the 1st day birth 50% of baby’s endogenous glucose comes from glycogenolysis During the 1st day of birth 35% of baby’s glucose comes from gluconeogenesis (glycerol, lactate, and alanine) Extrauterine Adaptation During the 1st hour of life the respiratory quotient changes from 1 to 0.8 suggesting a shift from glucose to a significant contribution by fat Adaptation is associated with hepatic release of glucose at 4 to 6 mg/kg/min Breastfed term have lower [glucose] but higher [ketones] than formula fed and tolerate lower [glucose] without clinical manifestations Brain and Glucose Metabolism Glucose is the main source of energy for the cerebral cells Glucose supply in the brain is regulated by [plasma] and the glucose transporter 1 (GLUT1) expressed in the brain and 3 (GLUT3) express in cerebellum Low plasma [glucose] activate counterregulation pathways with alternative fuels: pyruvate, lactate and ketones transported by monocarboxylate transporters Risk factors for neonatal hypoglycemia Decreased glucose reserve which includes pre-term babies Increased glucose utilization which includes babies with infection/fever Abnormal glucose regulation which includes babies with hyperinsulinemia and disorders of fatty acid oxidation. Glucose Screening Routine screening of AGA, at term, health and able to stay with their mother is not recommended Glucose screening of asymptomatic at risk infants may be performs at 2h and every 3-6h Symptomatic infants should be treated with IV glucose when blood glucose is less than 2.6 mmol/L Enteral supplementation may be used in asymptomatic infants when [glc] 1.8-2.5 mmol/L In each case, glucose levels should be checked every 30 minutes. Small for gestational age (SGA) infants and preterm infants may have inadequate glycogen stores making them at risk for neonatal hypoglycemia. For SGA infants and preterm infants, screening should be continued for 24h after birth Infants of diabetic mothers (IDM) are also at risk due to transient hyperinsulinemia. Similarly, large for gestational age (LGA) infants are presumed to have been exposed to elevated blood glucose levels in utero, resulting in hyperinsulinemia. For LGA infants and IDMs, screening should be continued for 12h after birth. Screening should occur every 3 to 6 hours before feeds after the initial 2-hour assessment. Screening should continue until the vulnerability period has elapsed or blood glucose levels remain >/= 2.6 mmol/L prior to feeds in the first 72 hours, (or 3.3 mmol/L beyond 72 hours). Any symptomatic or unwell infants should be immediately tested for hypoglycemia NH And Neurological Outcomes NH is associated with learning disabilities, CP seizure disorders, visual impairment and neurodevelopmental delay of varying degrees if: § Severe hypoglycemia 1 mmol/L § Persistent hypoglycemia (>2-3 hrs) Symptomatic: coma, seizures, hypothermia, apnea, cyanosis, and feeding poorly Jaundice Result of hyperbilirubinemia Yellow discoloration of skin/mucous membranes evident once bilirubin > 85mmol/L Progresses from: § Head (85mmol/L ® toes/soles (340mmol/L) Physiology of Bilirubin Metabolism RBC breakdown § Unconjugated/indirect bilirubin § Liver § Conjugated/direct bilirubin § Intestines § Stercobilinogen (excreted in stool) § Urobilinogen (reabsorbed into blood, excreted in urine) Unconjugated bilirubin cross BBB and is neurotoxic Conjugated not neurotoxic but indicates underlying serious disease Physiological Hyperbilirubinemia Occurs 2-3 days of life Pathophysiology of physiological hyperbilirubinemia: 1. Decreased RBC lifespan 2. Increased RBC mass and therefore breakdown 3. Immaturity of liver conjugation enzymes Pathological Hyperbilirubinemia hyperbilirubinemia is abnormal if it occurs less than 24hrs of life hyperbilirubinemia is abnormal if it occurs greater than 2-weeks of life Conjugated hyperbilirubinemia Excessive rate of rise > 85 mmol/L/24hr Causes of Unconjugated Hyperbilirubinemia in Neonates Bleeding/blood related RBC related/hemolysis Inadequate feeds/Breast feeding jaundice Breast milk jaundice Liver enzyme defect Hypothyroidism Increased enterohepatic circulation Causes of Unconjugated Hyperbilirubinemia in Neonates Bleeding/blood related § Birth trauma (cephalohematoma, bruising from breech delivery) § Hemorrhage (ie. Intraventricular) § Twin ® twin transfusion, maternal ® fetal, delayed cord clamping Causes of Unconjugated Hyperbilirubinemia in Neonates Bleeding/blood related RBC related/hemolysis § Blood Group Incompatibility: Rh incompatibility, ABO incompatibility (higher risk if mom O+ve) § Enzyme defect: G6PD (Asian males), PKD § Membrane abnormality: spherocytosis, elliptocytosis (osmotic fragility test) § Hemoglobin defect: SCD, thalassemia (alpha (4), Beta (2)) ® occur latter 4-6 months Causes of Unconjugated Hyperbilirubinemia in Neonates Bleeding/blood related RBC related/hemolysis Inadequate feeds/Breast feeding jaundice § Due to inadequate breast milk and dehydration Breast milk jaundice (day 10-14) § Breast milk thought to inhibit Glucuronyl transferase and activate glucuronidase Causes of Unconjugated Hyperbilirubinemia in Neonates Bleeding/blood related RBC related/hemolysis Inadequate feeds/Breast feeding jaundice Breast milk jaundice L Liver enzyme defect § Gilberts disease: decreased glucuronyl transferase activity § Crigler-Najjar syndrome: type 1 ® total lack of glucuronyl transferase type 2 ® partial deficiency Hypothyroidism Increased enterohepatic circulation § Due to infrequent stools, or bowel obstruction Causes of Conjugated Hyperbilirubinemia in Neonates Anatomical Hepatitis Inborn Errors of Metabolism Can develop: Dark/hyperpigmented urine Pale/acholic stools Causes of Cconjugated Hyperbilirubinemia in Neonates Anatomical § BILIARY ATRESIA: DO NOT MISS THIS (if operation early ® greatly increases survival) § Always do a bilirubin in kids who have jaundice at > 2 wks of age to r/o conjugated hyperbili and biliary atresia § Choledochal cyst Causes of Conjugated Hyperbilirubinemia in Neonates Anatomical: biliary atresia = DO NOT MISS. Hepatitis § Idiopathic neonatal § Infectious: CMV, Hep B, etc. § Toxic: sepsis, Total Parenteral Nutrition Inborn Errors of Metabolism § Hypothyroidism § Amino acid disorders § Cystic fibrosis § Storage diseases § Alpha 1 antitrypsin deficiency Kernicterus Deposition of unconjugated bilirubin in brain cells Early Signs: Lethargy, poor feeding, loss of moro reflex than decreases reflexes & respiratory distress Late Signs: § Opisthotonus, bulging fontanelle, twitching and high pitched cry Treatment of Jaundice Look at bilirubin graphs to see severity based on age and/or weight Also look at the velocity of change § Phototherapy § Exchange transfusion (if severe) Phototherapy Blue-green light (460-490 nm) is most effective The absorption of light by the normal bilirubin generates: § Configuration isomers § Structural isomers § Photooxidation products Configurational and structural isomers are more lipophilic than normal bilirubin and can be excreted in the bile without glucorinidation in the liver Photooxidation products are excreted mainly in urine Exchange Transfusion Involves slowly removing the babies blood and replacing it with fresh donor blood Complications: § Blood chemistry − Hyper-/hypo-kalemia, hypocalcemia, hypoglycemia, abnormal acid-base balance § Blood clots § Infection § Heart & lung problems § Shock − If insufficient blood