Neonatal Jaundice
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Transcript of Neonatal Jaundice
Neonatal Jaundice
Download more documents and slide shows on The Medical Post [ www.themedicalpost.net ]
Dr. Kalpana MallaMD Pediatrics
Manipal Teaching Hospital
• Incidence Term—60% Preterm—80%• Bilirubin Source – Hb – 75% Non Hb – 25% (Myoglobin)
Normal Physiology• Bilirubin -breakdown of hemoglobin• Unconjugated bilirubin (insoluble in water)
transported to liver- Bound to albumin • Transported into hepatocyte (Ligandin / y-
protein ) & conjugated - With glucuronic acid → now water soluble
• Secreted into bile
Normal Physiology
• Secreted into bile• In ileum & colon, converted to stercobilin • 10-20% (Deconjugated by β glucuronidase)
reabsorbed into portal circulation (Enterohepatic circulation )and re-excreted into bile or into urine by kidneys - urobilinogen
Bilirubin Metabolism
Glucuronyl TransferaseUnconjugated
(Bilirubin Diglucuronide)
NEWBORN JAUNDICE(PHYSIOLOGICAL)
Etiology1. Decreased RBC survival 90 days, increased RBC
vol /Kg, polycythemia of NB2. Poor hepatic uptake due to immature liver-
decreased ligandin or Y- protein3. Poor conjugation due to enzyme deficiency-
UDPG-T activity
NEWBORN JAUNDICE(PHYSIOLOGICAL)
4. Increased enterohepatic circulation due to - High level of intst beta-glucoronidase - delayed colonization by bacteria - Decreased gut motility5.Decreased hepatic excretion of bilirubin
PHYSIOLOGICAL JAUNDICE• Seen both in term and preterms
• Self limiting
• Develops after 24 hours
• Peaks by day 4- 5 in terms and day 7-8 in preterms
• Peak levels -12mg/dl in term & 15mg/dl in preterm
• Gradually subsides by 10-14 days
• No Treatment necessary
PATHOLOGICAL JAUNDICE
Suspect if...• Jaundice in first 24 hours• Rise of >5mg/24 hours or 0.5
mg/dl/hr• Jaundice beyond
physiological limits• Conjugated bilirubin- >2mg or
20% of total• Beyond 2 weeks• Signs of underlying illness ++
Pathological Jaundice - Hemolytic causes (unconjugated)
Coombs' test positive
–Rh incompatibility
–ABO incompatibility
Coombs' test negative
–Red blood cell membrane defects
–Red blood cell enzyme defects
–Drugs
–Hemoglobinopathies
–Sepsis
Pathological Jaundice - Non-hemolytic (unconjugated)
Extravascular sources
- cephalohematoma
- Polycythemia:- fetal-maternal
transfusion, - delayed cord
clamping- twin-twin
transfusion
Increased Enterohepatic circulation
– Cystic fibrosis– Ileal atresia– Hirschsprung's
disease– Breast milk
jaundice
Pathological Jaundice – Defective
Conjugation(unconjugated)
• Crigler-Najjar syndrome types 1 and 2
• Gilbert syndrome
• Hypothyroidism
• Breast milk jaundice
Pathological Jaundice – Defective Conjugation
Metabolic disorder:
• α1 AT deficiency
• Cystic fibrosis• Galactosemia • Gaucher's disease• Niemann-Pick
disease• Hypothyroidism
Chromosomal disorders
• Turner's syndrome,
• trisomy 18 and 21
Pathological Jaundice – Defective excretion
Biliary obstruction:• biliary atresia• choledochal cyst• Sclerosing
cholangitis • Dubin-Johnson
syndrome • Rotor's syndrome
Infection: • Sepsis• UTI• STORCH
infections
Causes of Jaundice –as per time of onset
Within 24 hrs• HDN—Rh, ABO Incompatibility• IU infections-CMV, HSV, Toxo, Syphilis• RBC Enzyme deficiencies-G-6PD defi, pyruvate kinase deficiency• Drugs—large dose of vit k , syntocin drip, Salicylates, sulphas etc• Hereditary Spherocytosis• Criggler-Najjar syndrome• Alpha thalassemia
24-72 hrs—Physiological Jaundice Exaggerated Physiological
Jaundice
(MATERNAL FACTORS)• -Blood type ABO or Rh incompatibility • -Breastfeeding
• -Drugs: Diazepam, Oxytocin
• -Maternal illness: gestational diabetes
Exaggerated Physiological Jaundice
(neonatal factors)• Birth trauma: cephalohematoma,
cutaneous bruising, instrumented delivery • Drugs: Erythromycin, Chloramphenicol • Immaturity ▪ Birth asphyxia Acidosis ▪ Cretinism
• Hypothermia • Hypoglycemia• Hypothyroidism • Polycythemia
After 72 hrs (within 2 weeks)
• Septicemia• Neonatal Hepatitis, other IU infections• Extra hepatic Biliary atresia• Breast milk jaundice• Metabolic diseases—galactosaemia, CF, alpha-
1 antitrypsin deficiency, hypothyroidism• Hypertrophic Pyloric stenosis
Diagnosis1)History—Antenatal Drugs Trauma Family H/O of jaundice Liver disease H/O delayed feeding Sepsis Sibling jaundice Splenectomy in family
2. General exam
• Cramer’s Index1.Face-4-6 mg/dl2.Chest &Upper trunk – 8-10 mg/dl3.Lower abdomen,thigh-12 -14mg/dl4.Forearms &lower legs -15 -18 mg/dl• Palms & sloes->15-20 mg/dl
Examine • Gestation age-preterm, IUGR• Cephalhematoma, bruising• Pallor-hemolytic anemia• Patechiea -sepsis, erythroblastosis, cong infections• HSM-hemolytic anemia, cong infections• Evidence of hypothyroidism, cong infections
3) Lab investigations
1. Hemoglobin, PCV with peripheral smear2. Total Bilirubin (Total / Direct & Indirect) - >12 mg /<24hr - <12 mg/ >24 hr3. Bilirubin level –Special tests –
– TORCH titres - Thyroid function tests
– Metabolic work up - Sepsis screen– USG / X ray abdomen
• Blood group and Rh typing• Reticulocyte count
Investigations in RH incompatibility
• Antenatal - (mother Rh-ve, previous baby Rh + ve, father Rh +ve.
1) H/o of abortion, H/o having taken Anti D gammaglobulin
2) USG for baby maturation ,HSM, ascites, hydrominos, gen. anasraca
Investigations in RH incompatibility
• Antenatal - - Blood grp (ABO & Rh) of father ,earlier baby - Indirect Coomb’s test – to detect antibodies in mother’s serumIgG Anti body Titre to D TO be estimated at 12-16,28-
32 and 36 weeks. If anti D antibody Titre 1:16 it should be tested serially
- Ab titre in mother’s blood ->1:64 dignostic of HDN- TO CONSIDER TERMINATION OF PREGNANCY.
Investigations in RH incompatibility
• Anmiocentesis:- Look for lecithin sphingomyelin ratio to suggest
maturity.- Shake test for 15 sec. with equal vol etanol 95%-
allowed to stand-ring of buble at the disc- Optical density-by spectrophotometer OD.>0.15
denotes maturity of lungs- Alpha feto protein level increased –rh issoimun- Fetal bloob grp prenatally – amniocentesis
POSTNATAL INVESTIGATION BABY
Cord blood—all babies of Rh-ve mothers, all Unknown blood groups, all with prior h/o jaundice in earlier babies
Blood group-both mother and baby - For evidence of hemolysis – Direct Coombs test Reticulocyte count - >10 suggest hemolysis. Hemoglobin cord Peripheral smear -RBC morphology Bilirubin
Others
RBC membrane defects• RBC enzymes –G-6-PD screenNeonatal hepatitis – LFTMetabolic studies – including hypothyroidismBiliary obstruction – USG,HIDA scan• PCV inc polycythaemia
Flow chart Jaundice >12mg/dl,age <24 hrs
<12mg/dl,age>24 hrs ↓ DCT............................. Negative ↓ ↓Positive Direct bilirubin ↓ >2mg/dlRh, ABO ,Others Hepatitis, TORCH, Sepsis, Biliary obstruction
Negative
Positive
Direct bilirubin < 2mg/dl Htc →high → polycythemia RBC Morpho, Retics ↓Abnormal NormalHemolytic A Breast milk J, Sepsis, IEMH.sperocytosis Hypothyroidism, asphyxia, ∝-
thalassemia physiologic J, DIC,Drugs ,ABO incom H.Pyloric stenosis
lowlow
MANAGEMENT
• Phototherapy• Drugs• Exchange
transfusion
MANAGEMENT OF JAUNDICE• To Decrease Bilirubin: -↑↑ excretion Phototherapy, ET - ↑↑ conjugation phenobarbitone - ↓ enterohepatic circ- Agar, Cholestyramine - Inhibit Bili production—metalloporphyrins - Inhibit haemolysis high dose IVIG - Inc albumin binding—Albumin
PHOTOTHERAPY
Phototherapy -MTH
Phototherapy -MTH
Phototherapy• Safe and effective method for
treatment of neonatal jaundice• Bilirubin absorbs light maximum at
420-460 nm
Mechanism of Action
Conversion of insoluble Bilirubin into soluble bilirubin
1.Photo-isomerization-conversion into soluble form – takes place in extravascular space of skin –conversion to less toxic polar isomer-diffuses into the blood –excreted easily into bile
2.Structural isomerization - conv to lumirubin -rapidly excreted in bile and urine
3. Photo-oxidation- of Bilirubin to water soluble polymers colourless by product.
Indications for Phototherapy
• TSB > 15 mg % in term• TSB > 12 mg% in preterm• TSB > 5 mg% within 24 hours• Adjuvant to exchange transfusion• Prophylactic PT – ELBW, bruised
babies, hemolytic disease of NB,VLBW with Perinatal risk factors
Indications
• Precautions– Cover the eyes and Genitals– Supplemental hydration– Watch for side effects
Procedure
• Best is narrow spectral blue lights (425-475nm)
• White lamps (380-700nm)• Distance from skin – 45cm
• Intensive PT – 15-20 cm• Shield eyes & genitalia• Space of 5-8cm between
phototherapy unit & incubator
• Double surface PT – can be given by fiber-optic blankets (biliblankets)
• Change position once in every 2-4 hrs
• Skin bleached by PT• Level to be checked every 10-20
hrs• Frequent temperature monitoring
& daily weight check
Side Effects
• Immediate – – Loose stools– Dehydration,– Hyperthermia,– ‘Bronze baby’ syndrome,– Rashes,– Upsets maternal infant interactions (bond)
• Late ––Risk of skin malignancies–Damage to intracellular DNA–Retinal damage–Disturbance in circadian rhythm Testicular damage
Biliblanket or glow-worm ?
Home phototherapy
DRUGS
• Phenobarbitone – increase y and z ligands
-induces liver ezymes - ↑↑ conjugation phenobarbitone
• Metalloporphyrins (tin and zinc porphyrins and meso prophyrins)
-inhibits heme oxygenase
• IVIG - Inhibit haemolysis• Oral agar, Cholestyramine-↓ enterohepatic
circ• Albumin infusionsInc albumin binding
• Exchange blood transfusion -- changing the babies blood with the other blood.
• Usually in hemolytic disease of newborn.
• It removes partially hemolysed and antibody coated RBCs and also billirubin
Methods of exchange
• Single volume exchange- 80ml/kg• Double volume exchange-
160ml/kg (87% of infant blood volume exchanged with new blood)
• Triple volume exchange.
Partial exchange transfusion
• Polycythemia• Chronic anemia with heart failure• Hydrops fetalis. • Observed pcv - desired pcv X 100 /
observed pcv.
Exchange Transfusion
Indications:• Rh and ABO incompatibility• Unconjugated billirubin > 20 -25mg/dl
in term, >15 -18mg/dl preterm babies. Sick neonates exchange at lower level
• Septicemia /DIC/ sclerema• Neonatal ITP• Severe anemia due to any cause with HF
Exchange Transfusion(Indications)
• Early Kernicterus• Cong H Sperocytosis• G-6- PD deficiency• Hepatic coma
In Hemolytic disease of the newborn (ABO / Rh)
• H/O previous severely affected infant• Cord Hb <10gm% & bilirubin > 5mg/dl• Rate of rise of bilirubun > 0.5mg/100ml/hr• Jaundice in first 24 hrs of life• Signs of hemolysis-clinical or lab• Maternal ab titer > 1in 64• Positive DCT• Preterm LBW with hyperbilirubinemia• Reticulocyte >10
Rh incompatibility• Due to Rh D-Ag• < 1 mL of Rh-positive fetal blood is sufficient to
sensitize the mother• 90% sensitization during delivery/abortion• So , most first born infants are not affected due
to the short period of exposure which is insufficient to produce a significant maternal Ig G antibody response.
Rh incompatibility
• Sensitized mother produces Ab –IgG types—crosses placenta
• Once sensitized –small doses of Ag stimulate high Ab titer .
• So, risk and severity of sensitization response increases with each subsequent pregnancy with Rh-positive blood fetus
ABO incompatibility• Mother is type O and the baby is either type A or
B. • O +ve Mothers makes antibodies which are IgM
& (IgG) types - IgG types crosses the placenta • No effects if the mother & baby have same blood
group or baby is grp O, as there is nothing to make antibodies against.
ABO incompatibility
• If mother - type A or B Makes antibodies (IgM) type so does not cross the placenta
So, even if baby has a different blood type no effect
Selection of blood
• Blood group O – no antigen Ab –anti -A, anti-B• Blood group A – antigen A Ab - Anti-B• Blood group B –antigen B Ab – anti -A
Blood for exchange transfusion
• Fresh CPD blood• Rh HDN-• ABO incompatibility -
Selection of blood • In Rh incompatibility: (O,A,B,AB-Negative) choice -Rh negative – - Preferably baby’s ABO - O group cross matched against
maternal serum• In ABO incompatibility – “O” blood group same as
baby’s Rh ( +/-) with low titre of Anti A and Anti B antibodies OR ABO type specific blood cross matched against infant serum
- Septicemia – Same as baby’s ABO and Rh
Investigations
• Pre exchange: Hb%, PCV, billirubin, glucose K+, Ca+.
• Post exchange: Hb%, PCV, billirubin, glucose, Calcium, K+, culture.
Procedure• IN NICU OR OT• Radiant warmer, Monitor HR, BP and
other vitals, infants arms and legs are restrained.
• Assistant to record volume in & out, to check vitals.
• Blood pre warmed to 37 c• Dried umbilical cord soaked with wet
gauze.• Canulation of umbilical vein- 12
o’clock
• Catheter inserted till free flow of blood or SHOULDER UMBILICAL LENGTH.
• Small aliquots of blood removed 5 to10ml -PUSH PULL method.
• Blood in the bag gently mixed.• Procedure over 1 to 2 hr. • Tie around the cord for 1 hr, or hold
tightly at the end of procedure.
Complications• Hypocalcemia and Hypomagnesemia -
Citrate in CPD blood.• Hypoglycemia• Metabolic alkalosis or acidosis.• Hyperkelemia.• CVS: overload and arrythmias• Infections: HBV HIV• Hemolysis• Hypothermia, NEC.
Other roots for exchange
• Umbilical vein cut down- incision above umbilicus in midline.
• Femoral vein canulation with radial artery canulation.
Guidelines for management of hyperbilirubenemia
Gestation and birth wt.
Phototherapy( healthy)
Exchange(healthy)
Phototherapy(sick)
Exchange(sick)
Preterm:
<1000gm. 5-7 11-13 4-7 10-12
1001-1500 7-10 13-15 6-8 11-13
1501-2000 10-12 15-18 8-10 13-15
2001-2500 12-15 18-20 10-12 15-18
Term:
2500 15-18 20-25 12-15 18-20
Breast milk jaundice
• Late onset• Due to factors in breast milk –Interfere with
bilirubin conjugation: - Pregnanediol - Free fatty acids - β-glucoronidase• Instead of ↓by 7 days it continues to rise may
go upto 20-30mg/dl by 2nd-3rd wks of age & return to normal by 4-12 wks
Management
• Stop breast feeding -48 hrs • Again resume it, bilirubin may rise again but
not reach previous high level
Breast feeding jaundice
• Decreased intake of milk leads to increased enterohepatic circulation
• Higher levels on day 4 compared to formula fed babies due decreased intake of milk
Prevention
1. Anti D to be given to the mother after delivery of the baby-within 48hrs. Also can be given to all unsensitized mothers at 28-32 weeks of gestation
2. Amniocentesis and IU transfusion to severely affected babies
3. Preterm delivery of severely affected babies4. Cord blood studies-followed by Phototherapy5. Exchange transfusion
KERNICTERUS
• Entry of unbound bilirubin into brain as free or albumin bound bilirubin
• Acidosis affects bilirubin solubility• Hyperosmolarity, anoxia and
hypercarbia disrupt BBB
• Yellow staining of brain assc with neuronal injury
• Affects basal ganglia, cranial nerve nuclei, brain stem nuclei, hippocampus and AHC of spinal cord (cortex usually spared)
• Necrosis, neuronal loss and gliosis …pathological findings
ACUTE BILIRUBIN ENCEPHALOPATHY
• STAGE 1: hypotonia, lethargy, high pitched cry and poor suck (D1-3)
• STAGE 2: hypertonia, opisthotonus, rigidity, oculogyric crisis, retrocollis, fever, seizures. (2nd week)
• Those who survive develop chronic bilirubin encephalopathy
• STAGE 3: Hypotonia replaces hypertonia after 3rd week age
CHRONIC BILIRUBIN ENCEPHALOPATHY
• Choreo-Athetosis• Partial or complete sensorineural
hearing loss• Limitation of upward gaze• Dental dysplasia• Intellectual deficits
LOW BILIRUBIN KERNICTERUS
• In LBW babies, preterms• Overt changes not seen• Other factors: IVH, drugs, benzyl
alcohol• More likely to suffer from anoxia,
hypercarbia and sepsis
TREATMENT
• Phototherapy• Exchange transfusion• Albumin infusion• Anticonvulsants: phenobarbitone• BERA at follow up
Neonatal cholestasis
Intrahepatic extrahepaticHepatocyte injury bile injury EH –biliary atresiametabolic viral intrahepatic bile duct paucity idiopathic neonatal hepatitis
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