Neonatal Jaundice (2).pdf---------------

neonatal

1. Neonatal jaundice
Presenters: Dr Anis Syazwani, Dr Lim Kgai Ying
Specialist: Dr Dinesh Nair

2. Introduction
-Most common condition in newborn
requiring medical attention
-Occur in 60% term and 80% preterm
-Significant jaundice occur in 6% of
term babies
-10% of breastfed babies are still
jaundice at 1 month of age
-Jaundice can be detected clinically
when the level of bilirubin in the
serum rises above
-85umol/L (5mg/dL)
Definition
-Jaundice is a yellowish
discoloration of the skin,
sclerae, mucous membrane and
nail from accumulation of
bilirubin
-Hyperbilirubinemia refers to
an excessive level of
accumulated bilirubin in the
blood and is characterised by
jaundice

3. Causes of hyperbilirubinemia
-Hemolysis due to ABO or Rh-isoimmunisation, G6PD
deficiency, spherocytosis or drugs
-Physiological jaundice
-Cephalohematoma or SAH
-Polycythemia
-Infection: septicemia, meningitis, UTI, intrauterine
infection
-Breastfeeding and breastmilk jaundice
-GIT obstruction: increase in enterohepatic circulation

4. Pathological Jaundice
-Appear within 24H of life
-Increase of bilirubin >
85umol/L
-Serum bilirubin > 255umol/L
-PROLONG JAUNDICE:
jaundice present after 14 days
in term infants and after 21
days in preterm infant
-Stool clay/white colored and dark
urine
-Direct bilirubin >34 umol/L
(2mg/dL)

Causes of pathological jaundice
-Hemolytic disease of newborn: Rh,
ABO and minor group incompatibility
ie anti-Kell, Duffy
-Infections: intrauterine be it viral or
bacterial
-Membrane defects: spherocytosis,
elliptocystosis, stomatocytosis
-Red blood cell enzyme defects: G6PD
deficiency, pyruvate kinase deficiency
-Polycythaemia

5. Physiological Jaundice
-Appears after 24H
-Maximum intensity by 3rd-5th day in
term and 7th day in preterm
-Serum level normally less than 255
umol/ L (15mg/dL)
-Clinically not detectable after 14 days
-No underlying cause
-Disappears without any treatment

Pathophysiology of hyperbilirubinemia
-Bilirubin is derived from the
breakdown of heme protein in
hemoglobin and myoglobin
-One gram of hemoglobin results in
the production of 34 mg of bilirubin
-Normal term newborn produces
about 6-10mg/kg/day of bilirubin

6. Metabolism of Hyperbilirubinemia
Bilirubin metabolism
-Bilirubin is bound to albumin for transport in the blood
-Bilirubin enters the liver cell and get bound to ligandin
-Conjugation occurs with glucuronic acid by glucuronosyltransferase to produce
mono and di-glucuronides which are water soluble (conjugated bilirubin is
water soluble)
-The conjugated bilirubin transported with the bile to the gut
-Enzyme, beta-glucuronidase converts bilirubin glucuronides into unconjugated
bilirubin which 95% is reabsorbed into the circulation (enterohepatic
circulation)
-Remaining conjugated bilirubin in the large intestine is metabolised by colonic
bacteria to form urobilinogen which is further oxidized to urobilin and
stercobilin

7. Pathophysiology of Physiological Jaundice
-Decrease erythrocyte life span (80-90 days) in a full term
infant
-Increase erythrocyte volume
-Increase bilirubin load on the hepatic cell
-Defective uptake from plasma into liver cells - decreased
ligandin
-Defective conjugation - relatively low activity of the enzyme
glucuronosyltransferase which normally converts
unconjugated bilirubin to conjugated bilirubin
-Low conversion of bilirubin to urobilinogen by the intestinal
flora resulting in higher enterohepatic circulation
-Decreased excretion

8. Breastfeeding vs Breastmilk Jaundice
Breastfeeding Jaundice
-Occurs in the first week of life
-Caesarean section infants more at risk due to lack of production of breastmilk
-Caused by insufficient breast milk intake resulting in inadequate quantities of bowel
movements to remove bilirubin from the body
-Resolved with increase feedings
-Breastfed babies are more likely to develop physiological jaundice within first week
of life.
Postulated theories:
-Inadequate breastfeeding leads to reduce intake
-Sluggish intestinal action leading to an increase in the enterohepatic circulation of
bilirubin
-Relative reduction of bilirubin levels in formula-fed babies due to increased clearance
of bilirubin from the gut

9. Breastfeeding vs Breastmilk Jaundice
Breastmilk Jaundice
-Indirect
hyperbilirubinemia in
a breastfed newborn
-Incidence during the
first 2-3 weeks - 36%
of breastfed infants
-Rarely causes
kernicterus
-Occur after the first
4-7 days of life and can
persist for 3-12 weeks

Breastmilk Jaundice
Pathophysiology
-Metabolite of progesterone (pregnane-3-alpha-20-beta-diol), a substance in
the breast milk that inhibits uridine diphosphoglucuronic acid (UDPGA)
glucuronyl transferase
-Increased concentration of non esterified fatty acids that inhibit hepatic
glucuronyl transferase
-Increased enterohepatic circulation of bilirubin due to increased content of
beta glucuronidase activity in breast milk and delayed establishment of
enteric flora in breastfed infants
-Defects in UDPGA activity in infants who are homozygous or heterozygous
for variants of the Gilbert syndrome promoter and coding region
polymorphism
-Inflammatory cytokines in human milk - interleukin IL-1 beta and IL-6 are
increased in individuals with breast milk jaundice and are known to be
cholestatic and reduce the uptake, metabolism and excretion of bilirubin

10. Risk factors
Risk factors for jaundice
- J - jaundice within 24 hours of life
- A - a sibling who was jaundiced as neonate
- U - unrecognised hemilysis
- N - non optimal sucking/nursing
- D - deficiency of G6PD
- I - infection
- C - cephalohematoma/bruising
- E - east asian/ north indian

Risk factors for severe NNJ
- Prematurity
- LBW
- Jaundice in the first 24 hours of life
- Mother with blood group O or rhesus negative
- G6PD deficiency
- Rapid rise of total serum bilirubin
- Sepsis
- Excessive weight loss
- Lactation failure in exclusive breastfeeding
- High predischarge bilirubin level
- Cephalohematoma or bruises
- Babies of diabetic mother
- FHx of severe NNJ in siblings

11. Prolonged Jaundice
Def: Visible jaundice (SB >85 umol/L) that persist beyond 14
days of life in term infants or 21 days in preterm infants.
Unconjugated hyperbilirubinemia Conjugated hyperbilirubinemia
- Septicemia or UTI
- Breast milk jaundice
- Hypothyroidism
- Hemolysis ie G6PD deficiency or congenital
spherocytosis
- Galactosemia
- Rare hereditary disorder of carbohydrate
metabolism that affect the body ability to convert
galactose to glucose
- Autosomal recessive genetic disorder
- Lactose intolerance
- Gilbert syndrome
- Biliary tree abnormality: biliary atresia (extra,
intrahepatic), choledochal cyst, paucity of bile ducts
(Alagille syndrome, non syndromic idiopathic
neonatal
hepatitis syndrome)
- Septicaemia or UTI
- Congenital infection (TORCHES)
- Metabolic disorders: citrin deficiency, alactosemia,
progressive familial intrahepatic cholestasis (PFIC),
alpha-1-antitrypsin deficiency
- Total parenteral nutrition
Causes of prolonged jaundice: unconjugated hyperbilirubinemia vs conjugated hyperbilirubinemia.

12. Clinical Approach to Jaundice
Approach to infant with jaundice
-History
-Age of onset
-Previous infant with jaundice, kernicterus,
neonatal death, G6PD deficiency
-Mother’s blood group
-Gestation: incidence of
hyperbilirubinemia increases with
prematurity
-Presence of abnormal symptoms such as
apnea, feeding adequacy, feed intolerance
and temperature instability

-The adequacy of breastfeeding, weight and hydration status of all babies should be assessed
during the first week of life
-Babies with weight loss > 6% of birth weight should be referred for further evaluation and closely
monitored for jaundice

13. Clinical Approach to Jaundice
Physical examination
-General condition, gestation and weight, signs of sepsis and
hydration status
-Signs of kernicterus: lethargy, hypotonia, seizure,
opisthotonus, high pitched cry
-Pallor, plethora, cephalohematoma, SAH
-Signs of intrauterine infection eg petechiae,
hepatosplenomegaly
-Cephalocaudal progression of severity of jaundice

14. Methods of detecting jaundice
1.Visual Assessment (Kramer’s rule)
2.Transcutaneous Bilirubinometer (TcB)
●if TcB levels are more than 200umol/l (12mg/dl), total
serum bilirubin (TSB) should be obtained.
●TcB is not to be used for patients on phototherapy.
3.Total Serum Bilirubin

15. Visual Assessment (Kramer’s rule)
• Based on the assessment of the extent and severity of
yellow discolouration of the skin
• It is performed by blanching the skin with slight finger
pressure and noting the underlying colour of the skin
• Jaundice is usually visible when bilirubin levels are about
5 - 7 mg/dL (86 - 120 µmol/L) and progresses from head to
toe as the level of bilirubin rises.
•Kramer’s rule describes the relationship between serum
bilirubin levels and the progression of skin discolouration

17. Complications

18. Investigation
1.G6PD testing (if not screened)
2.Mother’s and baby’s blood groups
3.A direct Coombs test
4.A full blood count ± peripheral blood picture
5.A reticulocyte count
6.A septic workup (if infection is suspected)
All babies should be screened for Glucose-6-phosphate dehydrogenase (G6PD)
deficiency. The results should be reviewed within 24 hours.
G6PD enzyme assays may be considered in babies suspected to have G6PD
deficiency but with normal/indeterminate Fluorescent Spot Test.

19. Management
●Phototherapy is the mainstay of treatment in NNJ. There are many types of
devices that can be used to provide phototherapy such as fluorescent tubes,
Light Emitting Diode (LED), fibreoptic and halogen bulbs.
●Phototherapy should be commenced when TSB reaches the phototherapy
threshold for neonatal jaundice
●Babies should be placed in the supine position with adequate exposure.
●Phototherapy should be started at a lower threshold in preterm and low birth
weight babies.
Once the baby is on phototherapy, visual observation as a means of monitoring is
unreliable. Serum bilirubin levels must guide the management

20. Prevention of severe neonatal jaundice
• All babies discharged <48H after birth should be seen by a healthcare provider in an ambulatory
setting or at home within 24H of discharge
• For babies with severe jaundice admitted for treatment, early follow-up is needed to detect rebound
jaundice after discharge
• Predischarge screening should be used to prevent severe neonatal jaundice (NNJ) in late preterm
and term babies
• Clinical risk factor assessment or/and predischarge bilirubin levels [transcutaneous bilirubin or total
serum bilirubin (TSB)] can be used as predischarge screening
• Universal predischarge bilirubin screening may be considered for all babies if resources are available
• All G6PD deficient babies should be admitted and monitored for NNJ during the first five days of life.
A TSB should be done if there is clinical jaundice
• Term G6PD deficient babies with BW > 2.5kg may be discharged earlier on day 4 of life if the TSB is
<160μmol/L (9mg/dL), and followed-up closely.

21. Exchange Transfusion
• Exchange transfusion (ET) is indicated for severe hyperbilirubinaemia
• Kernicterus has a 10% mortality and 70% long term morbidity
• Neonates with significant neonatal jaundice should be monitored closely and
treated with intensive phototherapy
• Mortality within 6 hours of ET ranged from zero death to 3 - 4 per 1000
exchanged term infants. Causes of death includes kernicterus itself, necrotising
enterocolitis, infection and procedure related events.

22. Indications of ET
Double volume exchange
•Blood exchange transfusion to lower serum bilirubin level and reduce the risk of brain damage associated with kernicterus
•Hyperammonemia
•To remove bacterial toxins in septicaemia
•To correct life-threatening electrolyte and fluid disorders in acute renal failure
Partial exchange transfusion
•To correct polycythaemia with hyperviscosity
•To correct severe anaemia without hypovolaemia.

23. Type of Blood to be used
•Rh isoimmunisation: ABO compatible, Rh negative blood
•Other conditions: Cross-match with baby and mother’s
blood
•In Emergencies if Blood type unkown (rarely): ‘O’ Rh
negative blood

24. Preparation of infant
• Signed Informed Consent from parent
• Ensure resuscitation equipment is ready and available
• Stabilise and maintain temperature, pulse and respiration
• Obtain peripheral venous access for maintenance IV fluids
• Proper gentle restraint
• Continue feeding the child. Omit only the LAST feed before ET
• If < 4 hours from last feed, empty gastric contents by NG aspiration before ET

25. •Volume to be exchanged is 2x the infant’s total blood volume (2x80mls/kg)
• Use (preferably irradiated) Fresh Whole Blood preferably < 5 days old or reconstituted Packed
Red Blood Cells and FFP in a ratio of 3:1
•Connect baby to a cardiac monitor
•Take baseline observations (either via monitor or manually) and record down on the Neonatal
Exchange Blood Transfusion Sheet.
•The following observations are recorded every 15 minutes: apex beat, respiration, oxygen
saturation
•Doctor performs the ET under aseptic technique using a gown and mask.
•Cannulate the umbilical vein to a depth of NOT > 5-7cm in a term infant for catheter tip to be
proximal to the portal sinus (for push-pull technique ET through UVC)
• Aliquot for removal and replacement – 5-6 mls/ kg (Not more than 5-8% of blood volume)
Maximum volume per cycle - 20 mls for term infants, not to exceed 5 ml/kg for ill or preterm
infants
• At the same time the nurse keeps a record of the amount of blood given or withdrawn, and
medications given

26. Investigation
Pre-exchange (1st volume of blood
removed)
•Serum Bilirubin
•FBC
•Blood C&S (via peripheral venous blood;
UVC to reduce contamination)
•HIV, Hepatitis B (baseline)
•Others as indicated
Post-exchange (Discard initial
blood remaining in UVC before
sampling)
•Serum Bilirubin
•FBC
•Capillary blood sugar
•Serum electrolytes and
Calcium
•Others as indicated

27. Post ET
•Maintain intensive phototherapy.
• Monitor vital signs: Hourly for 4 - 6
hours, and 4 hourly subsequently.
• Monitor capillary blood sugar:
Hourly for 2 hours following ET.
•Check serum Bilirubin: 4 - 6 hours
after ET.

Follow up
Long term follow-up to monitor
hearing and neurodevelopmental
assessment

28. THANK YOU