Extern Conference Thursday 27 th September 2007

History A preterm AGA 8 days old male infant with complaint of jaundice

History PI : the patient was born at weeks of gestational age (on 14 th sep 07) by spontaneous vertex delivery, with birth weight 2610 gm AGA, HC 32 (P 3-10 ) cm and body length 48 cm(P 3-10 ). Apgar scores were 10,10 at 1&5 minutes, respectively. Prenatal history was normal.

Maternal history His mother is 15-years old. G1P0A0. First ANC at GA 26 weeks x 4 times. Her blood group is B with Rh positive. Blood serology was all negative. Hct 35%, MCV 90 No family history of hematologic disease She came to the hospital with premature contraction, no PROM.

History On the 2 nd date of birth,he developed visible jaundice. Physical examination was unremarkable. GA 36 weeks by Ballard’s score. ABO and Rh blood types of the patient and his mother revealed no incompatibility. G-6-PD enzyme was normal. Coombs’ test was negative. Blood smear showed no hemolysis. Reticulocyte count was 7.22

History At that time, phototherapy was started and continued for 4 days. The microbilirubin was declined. He was discharged home on 18 th sep 07, the 5 th day of birth. BW was 2560 gm on the discharged day.

History After discharge home (DOL 3D21HR), he was given only breast feeding, about 10 times per day, 20 minutes each feed. Frequency of urination was 10 times per day, yellowish color. Frequency of defecation was 3-4 times per day, yellowish color

History On the admission day (DOL=7), his mother brought him to Siriraj hospital to follow up his jaundice clinical. He had no fever, active but still icteric.

History Diet : breast feeding only Immunization : HBV, BCG at birth No history of neonatal jaundice in family

Physical examination V/S : T 37c, BP 55/35mmHg,RR 54/min, PR 141/min BW 2470 gm HC 32 cm BL 48 cm GA : active, mildly pale, marked jaundice, no petechiae or rash, no dyspnea. HEENT : no cephalhematoma, no macroglossia, no tongue tie, AF 2x3 cm,PF 1x1 cm Eyes : no cataract,cornea clear CVS : normal s1 and s2, no murmur RS : normal breath sound, no adventitious sound.

Abdomen : soft, no distention, bowel sound positive, liver and spleen can’t be palpated. CNS : normal reflexes, normal muscle tone Physical examination

Problem list Maternal teenage pregnancy Preterm AGA male infant, NL, BW 2610 g, Apgar 10,10 History of visible jaundice on 2 nd day of life with phototherapy treatment for 4 days Recurrent visible jaundice on DOL 7

Neonatal jaundice A yellow discoloration of the skin, mucous membrane, and sclera in the first 4 weeks of life after birth. Neonatal jaundice is visible when total serum bilirubin exceeds 5 mg/dl

Physiologic jaundicePathologic jaundice After 48 hr of lifeIn 24 hr or after 2 wk Total serum bilirubin < 12 mg/dl (term) < 15 mg/dl (preterm)  < 5 mg/dl/d Total serum bilirubin > 12 mg/dl (term) > 15 mg/dl (preterm)  > 5 mg/dl/d Persist  7 d of age (term)  14 d of age (preterm) Persist > 14 d of age (term) > 21 d of age (preterm)

Common disease in neonatal jaundice Unconjugated hyperbilirubinemia Conjugated hyperbilirubinemia Hemolytic disease of the new born G-6-PD deficiency Sepsis Breast feeding / Breast milk jaundice Extravasation Biliary atresia Neonatal hepatitis

Pathology Bilirubin production Hemolysis Extravasation Bilirubin conjugation Impaired hepatic function Bilirubin excretion Biliary tract obstruction Intestinal obstruction Increase enterohepatic circulation

In this patient DDX Hemolytic jaundice Breast feeding jaundice

Investigation CBC with slide TB/DB/MB reticulocyte count TSH Coombs’ test G6PD Blood group normal

Investigation (21/9/07) The blood examination was performed. Microbilirubin : 21.4 mg/dL. TB : 26.2 DB : 2.5 CBC : Hb 9.8 Hct 27.4% WBC 9440 (N 46% L 49% M 3% E 2%) Plt MCV 83 RDW 18.1 anisocytosis 1+ poikilocytosis 1+ reticulocyte count 3.11 ( ) TSH 3.08 mcu/ml (0-18)

Review blood smear Normochromic normocytic RBC Anisocytosis 2+, poikilocytosis 1+, polychromasia few spherocyte 2+ WBC no band form Platelets adequate

Problem list Maternal teenage pregnancy Preterm AGA male infant, NL, BW 2610 g, Apgar 10,10 History of visible jaundice on 2 nd day of life with phototherapy treatment for 4 days Recurrent visible jaundice on DOL 7 anemia

Neonatal jaundice Direct hyperbilirubinemiaIndirect hyperbilirubinemia Neonatal hepatitis - Intrauterine infection Biliary atresia Sepsis etc Coombs’ Test,Blood types NegativePositive Dx:Isoimmunization Rh ABO Other Hemoglobin or Hct Low or normalHigh

Coombs’ test negative Low or normalHigh Dx: Polycythemia Maternal-fetal transfusion Twin-twin transfusion Delay cord clamping Intrauterine hypoxia Reticulocyte count Normal High RBC morphology Dx:- Physiologic jaundice -Extravascular blood in body tissue -Increase enterohepatic circulation -Breast milk jaundice -Hypothyroidism -Metabolic errors -Hormone+drugs Abnormal Non-specific Diagnostic Dx : -RBC abnormality -Hemoglobinopathy -Enzyme deficiency -Hemolysis -DIC /sepsis Dx: -Spherocytosis -Elliptocytosis -Stomatocytosis -Pyknocytosis Hemoglobin or Hct

DDx Hemolytic jaundice Breast feeding jaundice

DDx Hemolytic jaundice

Most likely diagnosis Indirect hyperbilirubinemia from hemolysis -HS -Thalassemia

Goals Prevention of kernicterus Treatment of underlying conditions Maintenance of hydration and nutrition Interventions Intensive Phototherapy Exchange transfusion Treatment

Indication for early phototherapy Bilirubin rising faster than 0.5mg/dL/hr or 5mg/dL/d Persistent, severe metabolic or respiratory acidosis Sepsis Sick VLBW infants Indication for phototherapy in infants >35 weeks gestation AAP: Clinical Practice Guideline: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks Gestation, July 2004 Phototherapy

In this case

Indication in infants 35 weeks gestation or more Exchange transfusion

In this patient Double phototherapy Hct/MB : 32/ hours Hct/MB : 32/22.7 Exchange transfusion Pre-transfusion : Hct/MB 21/15.4 Post-transfusion : Hct/MB 31/8.9

Action Replacement of the neonate’s blood with donor blood that has normal level of serum bilirubin Mechanism: removes bilirubin and antibodies from circulation and correct anemia Most beneficial to infants with hemolysis Generally never used until after intensive phototherapy attempted Exchange transfusion

Indication Intensive phototherapy fails TB exceed the level indicated in guideline Despite intensive phototherapy for 6 hrs Signs of acute bilirubin encephalopathy

Principle of exchange transfusion Two-volume exchange (160 ml/kg) Push-pull method (5 ml/kg/2-3min) Time min In case of blood group incompatibility, choose bl gr. which compatible with both mom and baby.

Complication PhototherapyExchange transfusion Tanning, Bronze baby syndrome, lactose intolerance hemolysis, skin burns, dehydration, skin rashes Diarrhea Retinal Change *prevent by shielding eyes from light Riboflavin deficiency (occur in prolongd phototherapy) * prevent by daily riboflavin intake of 0.3 mg. From the procedure. Embolization with air or thrombi, thrombosis, arrythmia, overheparinization, apnea, bradycardia, cyanosis, vasospasm, hypothermia, volume overload, arrest, From blood products. Hyperkalemia, hypernatremia, hypocalcemia, acidosis, coagulation disturbance, blood-borne infections. *Monitoring of electrolytes, platelet count, coagulation parameters, and arterial blood gases is recommended.

Progression Date and timeHct /MBNutritional status 22/9/07 : 7D18Hr 45/12.5 (15)NPO 10%D/N/5 22/9/07 : 8D 46/11.1 (15)BM/SI 22/9/07 : 8D10Hr 44/11.6 (15)BM/SI 23/9/07 : 8D23Hr 39/7.5 (15) Off photo BM/SI

Progression Date and timeHct /MBNutritional status 23/9/07: 9D11Hr 39/9.1BM/SI 24/9/07: 10D3Hr 43/8.9BM/SI

Plan of management Continue breast feeding Consult hematologist to find out the cause of hemolytic anemia -Inclusion body test : negative -Hb typing : pending Observe clinical of kernicterus

Complication of neonatal jaundice Acute bilirubin encephalopathy The acute manifestations of bilirubin toxicity in the 1 st week after birth. Early phase: lethargic and hypotonic Intermediate phase: stupor, irritability, high pitched cry fever, hypertonia Advance phase: Retrocollis-opisthotonos, shrill cry, apnea, coma, sometimes seizure and death Kernicterus The chronic and permanent clinical sequelae of bilirubin toxicity

Discharge Assessment before discharge Predischarge bilirubin Use nomogram to determine risk zone Assessment of risk factors TSB Zone before dischargeNewborns n (%) Newborns Who Subsequently Developed a TSB Level > 95th Percentile, n (%) High-risk zone639.5 High intermediate-risk zone Low intermediate-risk zone Low-risk zone61.80

Discharge Assessment before discharge Predischarge bilirubin Use nomogram to determine risk zone Assessment of risk factors TSB Zone before dischargeNewborns n (%) Newborns Who Subsequently Developed a TSB Level > 95th Percentile, n (%) High-risk zone639.5 High intermediate-risk zone Low intermediate-risk zone Low-risk zone61.80

Follow-up Care Plan based on Age in hours at discharge Risk of excessive hyperbilirubinemia Availability and reliability of follow-up

Infant DischargedShould be Seen by age Before age 24 hours 72 hours Between hours 96 hours Between hours 120 hours Follow-up Care Timing of follow-up

Follow up assessment should include Body weight, % change from BW, adequacy of intake, the pattern of voiding and stooling, presence or absence of jaundice Clinical judgment should be used to determine the need for a bilirubin measurement. If there is any doubt about the degree of jaundice. Blood testing should be done. Follow-up Care

Some harmful advice and beliefs have to be changed. All health personnel should not advise parents to supplement water or dextrose water to newborns or expose newborns to sunlight. Follow-up Care

Parents should be educated and provided with adequate educational materials at discharge regarding jaundice, feeding adequacy and symptoms to watch for, the risks of untreated hyperbilirubinemia, and the need for close follow-up of their infants after discharge Follow-up Care

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