26. NEONATAL JAUNDICE LECTURE FOR MEDICAL STUDENTS.pptx

neonatal jaundice

1. NEONATAL JAUNDICE ILOH, KENECHUKWU K. MBBS, DIP(THEO), FMCPaed, FWACP

2. LEARNING OBJECTIVES Define hyperbilirubinemia Metabolism of bilirubin Differentiate between physiological and pathological jaundice State the causes of hyperbilirubinemia Discuss the complication of hyperbilirubinemia Therapeutic management

3. BACKGROUND Jaundice is the most common condition that requires medical attention in newborns. Approximately, 85% of all term neonates and most preterms develop clinical jaundice. The yellow coloration of the skin, sclera and mucous membranes in newborns with jaundice is the result of accumulation of bilirubin In most infants, it reflects a normal transitional phenomenon. U nconjugated bilirubin is neurotoxic and can cause death in newborns and lifelong neurologic sequelae in infants who survive Every jaundice must be observed/investigated.

4. Normal adult bilirubin level is <1mg/dl and jaundice develop when serum bilirubin exceeds 2mg/dl. In neonates, jaundice appear at > 5mg/dl. Jaundice progresses in a cephalo-caudal direction. Unconjugated bilirubin – indirect bilirubin C onjugated bilirubin – direct bilirubin

5. SOURCES OF BILIRUBIN Bilirubin is derived from the breakdown of heme -containing proteins in the RES. A normal newborn produces about 6-10mg bilirubin /kg/day.{adults:3-4/kg/day} The major heme -containing protein is the RBCs contributing 75% of bilirubin production. One gram of haemoglobin produces 34mg of bilirubin. 25% of bilirubin come from myoglobin, cytochromes, catalase, peroxidase and free heme .

6. BILIRUBIN METABOLISM Production: Heme Biliverdin ( heme oxygenase ) Fe + Co (re-utilized) (excreted) ( biliverdin reductase ) Bilirubin

7. BILIRUBIN METABOLISM CONTD Transport : bound to albumin and transported to the liver. Uptake : dissociates from albumin, bound to cytoplasmic Ligandin (Y protein) for transport into the smooth endoplasmic reticulum . Conjugation : bilirubin is converted to water soluble form by uridine diphosphogluconurate glucuronosyltransferase (UGT). Conjugation can be to mono or diglucuronides ; both are water soluble and are excreted into bile canaliculi via a concentration gradient.

8. BILIRUBIN METABOLISM CONTD. Excretion : CB from the biliary tree enters the GI tract and eliminated in the stool. CB is converted to UCB by intestinal enzyme β - glucuronidase and delivered back to the liver for reconjugation in a process called entero -hepatic circulation. Intestinal bacteria prevent this process by converting CB to urobilinoids which are not substrates for β - glucuronidase

9. PHYSIOLOGY OF BILIRUBIN

10. CLASSIFICATION

11. MECHANISMS OF PHYSIOLOGICAL JAUNDICE Increased Bilirubin production - Increased RBCs volume per kilogram -Decreased RBCs survival (90 days) -Increased ineffective erythropoiesis -Increased turn over of nonhemoglobin heme proteins Increased entero -hepatic circulation - high level of β - glucuronidase -decreased intestinal bacteria -decreased gut motility -poor evacuation of meconium -preponderance of bilirubin monoglucuronide

12. MECHANISMS OF PHYSIOLOGICAL JAUNDICE CONTD Defective uptake -decreased ligandin -binding of ligandin by other ions. Defective conjugation due to decreases UGT activities Decreased hepatic excretion of bilirubin.

13. CAUSES OF NEONATAL HYPERBILIRUBINEMIA Overproduction (unconjugated hyperbilirubinemia) - ABO, RH- isoimmunization -G6PD deficiency -Hereditary spherocytosis, elliptocytosis , somatocytosis -Other red cell enzyme deficiencies -Extravascular blood like petechiae , hematomas, pulmonary, cerebral or occult hemorrhage - Polycythemia -Increased enterohepatic circulation.

14. CAUSES OF NEONATAL HYPERBILIRUBINEMIA Under-secretion (conjugated hyperbilirubinemia) Metabolic conditions like galactosemia , Crigler-Najjar syndrome type 1 and 2,Gilbert disease, Tyrosinosis , Lucey-Driscoll syndrome. Endocrine disorders like hypothyroidism, hypopituitarism, infant of diabetic mother, anencephaly Obstructive disorders like biliary atrsia , choledochal cyst, Dubin -Johnson syndrome, Rotor syndrome, cystic fibrosis and α 1-antitrypsin deficiency and total parenteral nutrition.

15. CAUSES OF NEONATAL HYPERBILIRUBINEMIA Mixed -sepsis -TORCH -Intra uterine infections; syphilis, hepatitis -Respiratory distress syndrome -Hypoxia-ischemia -Infant of diabetic mother

16. Common Causes of Jaundice A – ABO Incompatibility G – Glucose-6-phosphate dehydrogenase deficiency I – Infections/sepsis P – Prematurity O - Others

17. EVALUATION OF NEONATAL JAUNDICE

18. PHOTOTHERAPY The most effective light for phototherapy is the blue light (wave length 420-470nm ). When bilirubin absorbs light, three reactions occur to convert bilirubin to the water soluble form; - photo-isomerization -structural isomerization to lumirubin (2-6%) - photo-oxidation

19. INDICATION FOR PHOTOTHERAPY When the level may be hazardous if it were to increase. Prophylactic phototherapy when UCB is expected to increase. It is contraindicated when it is CB.

20. TECHNIQUE Effective phototherapy depends on - spectrum of light (430-490nm) -irradiance (energy output) = 8-10µW/cm²nm -distance above infant = 20cm Infant under phototherapy should be naked except for eye patch and cover for the perineum. Side effects include increased insensible loss, diarrhoea , retinal damage, over-heating, rashes, loose stools, bronze baby syndrome

21. The therapeutic effect depends on:- The light energy emitted on in the effective wavelengths. The distance between the lights & the infants. The amount of skin exposed. The rate of hemolysis if present. Rate of metabolism & excretion of bilirubin.

22. EXCHANGE BLOOD TRANSFUSION It removes partially hemolyzed and anti-body coated RBCs as well as unattached antibodies in addition to the unconjugated bilirubin. Indications include - failure of phototherapy -to stop hemolysis and bilirubin production by removing antibodies and sensitized RBCs. -if cord bilirubin level > 4.5mg/dl and cord Hb <11g/dl .

23. EXCHANGE BLOOD TRANSFUSION Bilirubin level rising >1mg/dl/hr despite phototherapy Bilirubin level rising >0.5mg/dl and Hb level is between 11-13g/dl despite phototherapy Bilirubin level is 20mg/dl or will soon reach 20mg/dl at the it is rising Bilirubin level 5mg/dl/24hrs

24. TECHNIQUE OF EBT An aseptic procedure Fresh blood is used(<7days), irradiated, pcv 45-50% In Rh iso - immunization, crossmatch type O Rh – ve blood with mother and infant. ABO incompactibility , crossmatch type O Rh – ve or Rh compactible with mother and infant. Double volume exchange Procedure should not exceed 90 minutes, ideal duration is 60minutes.

25. COMPLICATIONS OF EBT Hypocalcemia Hypomagnesemia Hypoglycemia Hyperkalemia Cardiovascular; arrhythmias, air/thromboembolism, infarction and overload Infections; HIV, HepatitisB&C , CMV, malaria Hemolysis Graft versus Host disease Hyper/hypothermia, possibly NEC.

26. BILIRUBIN TOXICITY Acute bilirubin encephalopathy: clinical manifestation of bilirubin toxicity seen in the neonatal period. Divided into 3 phases - Early phase : hypotonia, lethargy, poor suck, high-pitched cry. - Intermediate phase :hypertonia of extensor muscles ( opisthotonus , rigidity, oculogyric crisis and retrocolis), irritability, fever and seizures. (most infant die at this stage. Survivors develop chronic bilirubin encephalopathy). Advanced phase :pronounced opisthotonus , shrill cry, apnea, seizures and death .

27. BILIRUBIN TOXICITY UCB crosses the a disrupted BBB as free bilirubin or bound to albumin.(factors that disrupt BBB include hyperosmolarity , asphyxia, acidosis, hypercarbia Kernicterus is a pathological diagnosis, it refers to the yellow staining of the brain with evidence of neuronal injury seen in basal ganglia, cerebellar nuclei, and hyppocampus . Chronic bilirubin encephalopathy (kernicterus) is marked by (cerebral palsy) athetosis , sensineural deafness, upward gaze paralysis, dental hyperplasia and intellectual deficits.

28. Breast milk jaundice F irst described in 1963. Arias et al. noted that some breastfed infants had unconjugated hyperbilirubinemia that persisted beyond the third week of life.  T ypically presents in the first or second week of life and usually spontaneously resolves even without discontinuation of breastfeeding. However , it can persist for 8-12 weeks of life before resolution. Pathological causes of unconjugated hyperbilirubinemia should be ruled out before a breast milk jaundice diagnosis can be made.

29. The etiology of breast milk jaundice is not clearly understood, but a combination of genetic and environmental factors may play a role. Most of the proposed etiologies involve the factors present in the human breast milk itself.  These factors that may be related to breast milk include pregnane-3a,20ß-diol, interleukin IL1ß, ß-glucuronidase, epidermal growth factor, and alpha-fetoprotein . Inhibits bilirubin's conjugation, impede bilirubin excretion, deconjugates bilirubin, cholestatic effect and increased enterohepatic circulation.

30. Treatment is not necessary unless the infant's total serum bilirubin level is greater than the phototherapy guidelines. If the total serum bilirubin level remains below 12 mg/ dL , the recommendation is to continue breastfeeding. If the total serum bilirubin level is higher than 12 mg/ dL but below the phototherapy level, and further investigation shows no hemolysis evidence, the recommendations are also to continue breastfeeding. When the bilirubin is greater than 20, a brief 24-hour cessation of breastfeeding may be beneficial.

31. Breastfeeding jaundice usually occurs in the first week of life while the baby and mother are in the early stages of learning how to breastfeed. The result of the baby not receiving enough milk to lower their bilirubin levels. This causes the bilirubin to be reabsorbed into the intestines and keep the levels elevated which triggers jaundice – Increased Enterohepatic Circulation. A baby's  meconium  (early bowel movements) are also essential to helping remove bilirubin, and inadequate milk supply delays the passage of meconium .

32. Breastfeeding jaundice can occur when a newborn does not get a good start on breastfeeding supplemented with other substitutes that interfere with breastfeeding improper latching poor positioning. Treatment for this condition is fairly simple, and there is no need to stop breastfeeding. The mother should increase the number of feedings per day and work with a  lactation consultant  to make sure the baby is receiving the right amount of milk each time.

33. THANKS FOR YOUR ATTENTION