1. Interesting Case Rounds
July 31, 2008
Sean Caine
CCFP-EM Resident

2. The Case
90 d F referred from urgent care for FTT and prolonged jaundice

4. History

5. History Pregnancy Delivery
Mother was 23 yo Caucasian female G1P0 O neg
Routine serology was normal
GBS negative
Nonsmoker. No EtOH
Uncomplicated pregnancy (no PIH or GDM)
Delivery
39wks GA
ROM x 3 hrs
BW=3220
Apgar 91,95
DAT negative
Newborn metabolic screen was normal
Tbili at discharge =190
d/c home 24hrs postpartum
Consider pointing out tbili on nomogram

6. History Followed by GP qweekly x 6 wks
Jaundiced noted again at 6wk follow up with maternity care clinic
1 oz wt loss in past month
Exclusively breast fed. Feeds well.
~6-8 BM/day. Stools are typically yellow. Recently have become more pale.
~6-8 wet diapers/day. Urine is brown.
ROS otherwise unremarkable for sleep, appetite, activity, or symptoms indicative of focus for infection etc

7. On exam
VS: /47 36
No apparent distress. Awake. Alert. Interactive and pleasant
++scleral icterus. +jaundice
Firm liver edge. Palpable spleen tip.
CV, Resp, CNS, Abdo exam otherwise unremarkable

8. Labs/Investigations

9. Labs/Investigations CBC LFT/enzymes Ammonia 61 H (12-47)
Hb 110 (90-140)
WBC 21.5 H (5-19.5)
Plt 569 H ( )
Neut 9.2 H (1-9)
Lytes, Cr, Urea – NORMAL
Urinalysis/R&M
LARGE Leuks,
SMALL blood
20-30 WBC/hpf
0-5 RBC
Few bacteria
LFT/enzymes
Tbili 178 H (0-23)
Direct bili 118 H (0-7)
ALT 199 H (1-35)
AST 262 H (10-65)
ALP 461 H (40-390)
GGT 796 H (8-35)
Albumin 38
INR 1.1
PTT 40.5 H (27-36)
Ammonia 61 H (12-47)
Bottom line: Conjugated hyperbilirubinemia in 3 month old infant with elevated lever enzymes and urinalysis consistent with UTI

10. Objectives Review features of physiologic and pathologic jaundice
Review approach to neonatal cholestasis
Highlight some common pitfalls
Return to the case to review the work up and diagnosis

11. Hyperbilirubinemia
Has increasingly become a presenting complaint to ER due to early postpartum discharge
However, still rare to encounter in Calgary ER
Screened by PHN/GP in first 3-5 days postpartum
Direct admit to PLC Unit 31 for assessment +/- phototherapy
Very common problem. Often benign and easy to become complacent about. Thought it would be worthwhile to review as although rare to encounter in ER here, very common problem, and may be encountered more frequently outside the CHR . In particular for our FRCP residents who will be unlikely to encounter this at AC. Even though patients are sent to PLC, they typically bypass ER and are directly assessed on the floor.

12. Hyperbilirubinemia

13. Physiologic vs. Pathologic Jaundice in the Newborn

14. Physiologic vs. Pathologic Jaundice in the Newborn1
Unconjugated hyperbilirubinmia
60% term & >80% preterm neonates in first week
Rises at rate <85 umol/L/day
Appears on 2nd or 3rd day of life
Typically peaks btwn days 2-4
Begins to decline on days 5-7 at rate of 34 umol/L/day
Pathologic
Appears <24 hrs
Excessive for infant’s age (Tbili > 205 umol/L)
Elevated direct bilirubin
Jaundice present at or beyond 3 wks
Sick infant
Tbili rising >85 umol/L/day
Unexplained jaundice following phototherapy
Jaundice in the presence of risk factors
Cover etiology of physiologic jaundice.
Recognize that there is overlap. In particular with the timeline as sepsis, metabolic disorder (G6PD or PK deficiency). But they will be accompanied by story of unexplained irritability, feeding difficulties, hypotonia, lethargy, seizure, fever etc.
Recent studies suggest that clinical examination is poor predictor of severity of jaundice
This info is direct from the AAP guidelines. The same guidelines Dr. Jorgenson made sure to provide each family resident and all to eagerly review at 3-4 in the morning.

15. Ddx Conjugated vs. Unconjugated Hyperbilirubinemia
Physiologic
Pathologic
Hepatic
Infectious
Sepsis
Hep B, TORCH
Metabolic
Galactosemia
Tyrosinemia
Alpha-1-antitrypsin
Hypothyroidism CF
Drugs
TPN
Idiopathic neonatal
Cholestasis
Bile duct paucity
AbN Bile acid metabolism
Extra Hepatic
Biliary atresia
Choledocal cyst
Non-hemolytic
Cephalohematoma
Polycythemia
Sepsis
Hypothyrodism
Gilbert’s
Crigler- Najjar
Hemolytic Extrinsic
Immune
ABO-incompatibility
Rh-incompatibility
Kelly-Duffy etc
Non immune
Splenomegaly
Sepsis
AV malformation
Hemolytic Intrinsic
Membrane
Spherocytosis
Elliptocytosis
Enzyme
G6PD
PK deficiency
Hemoglobin
Alpha thal

16. Ddx of Hyperbilirubinemia According to Time of Onset
First 24 hours
24-72 hours
72-96 hours
> 1 week
Often pathologic
Hemolysis (Rh
or ABO)
Sepsis (GBS,
TORCH)
Cephalohematoma
Spherocytosis
Hemorrhagic
disease of the
newborn
Often pathologic
Breast milk jaundice
Prolonged
Physiologic
Hypothyroidism
Neonatal
Hepatitis
Galactosemia
Familial
Cholestasis
Biliary atresia
Paucity of bile
ducts
Physiologic
Polycythemia
Dehydration
Hemolysis
G6PD
PK def
Cephalohematoma
Spherocytosis
Sepsis/TORCH
Physiologic
Dehydration
Sepsis
Gilbert’s
Crigler-Najjar
Hypoxia/resp
distress/hypoG

17. Neonatal Cholestasis
Defined as the impaired canalicular biliary flow resulting in acumulation of biliary substances (bilirubin, bile acids, and cholesterol)2
Estimated incidence of 1/2500 live births
Jaundice at 2-3 weeks of age increases suspicion2
2.4-15% of newborns are jaundice at 2 weeks of age6
Estimated that jaundiced infants at 2 weeks of age would need to be tested to detect one case of cholestasis 26

18. Common Pitfalls Breast feeding jaundice Breast milk jaundice
Exaggeration of physiologic jaundice
Day 2  7
Premature babies: can last up to 10 days
Breast milk jaundice
2% of breast fed babies
Starts ~ day 7, persists until week 2-3
May persist for 3-10 weeks at low levels
Unconjugated
Theory: glucuronidase in breast milk  increased enterohepatic bilirubin re-circulation

19. Neonatal Cholestasis Clinical Presentation Prolonged jaundice
Pale stools
Dark urine
Coagulopathy
Hepatomegaly
Splenomegaly
RUQ mass
FTT
Less specific suggestive of underlying
metabolic, CNS, or infectious aetiology:
Fever
Irritability
Lethargy,
Seizures
Poor feeding
Dysmorphic features

20. Ddx Neonatal Cholestasis
Infectious
Bacterial
Protozoal
TORCH
Echovirus
Adenovirus
Parvovirus B18
Obstruction
Biliary Atresia
Choledochol cyst
Tumor
Inspissated bile/plug sybdrome
Gallstone
Biliary Sludge
Metabolic/Genetic
Alagille Syndrome
α-1-Antitrypsin
Galactosemia
Tyrisonemia
Lipid metabolism disorders
Bilae acid metabolism disorders
Mitochondrial Disease
Citrin deficiancy

21. Approach to Neonatal Cholestasis
Initial investigations: Establish cholestasis and determine severity of disease
Detailed hx, exam
Fractioned serum bili
Tests for liver injury (AST, ALT, ALP, GGT)
LFT (Albumin, INR, PTT, serum ammonia, glucose)
Detect conditions that require immediate treatment
CBC, blood & urine cultures to r/o sepsis
Serum T4 and TSH
Metabolic Screen: lactate, ammonia, iron, ferritin, urinalysis, urine amino acids and organic acids
Viral serologies, VDRL, and cultures

22. Approach to Neonatal Cholestasis
Differentiate extrahepatic disorders from intrahepatic causes of cholestasis
U/S
Hepatobiliary scintigraphy
Perc liver bx,
Exploratory laparotomy with intraoperative
Establish other specific diagnosis
α-1-antitrypsin, CF, Alagille, PFIC, storage disorders

23. Back to the Case Initial investigation: establish cholestasis
Detect conditions that require treatment
Differentiate extrahepatic disorders from intrahepatic causes of cholestasis
Investigate for the rare diagnosis

24. BiliaryAtresia
Inflammation of bile ducts leading to progressive obliteration of the extrahepatic biliary tract
Most common cause of cholestasis in the first few weeks of life
Incidence of 1/10,000 to 1/20,000 births
Cause remains unknown though various infectious (CMV, reovirus, rotavirus) and genetic causes have been proposed

25. Biliary Atresia Jaundice typically develops in weeks 3-6
Uncommon for jaundice to be present at birth
10-15% association with congenital malformations (polysplenia, malrotation, etc)

26. Biliary Atresia Diagnosis U/S can be suggestive
Liver biopsy is the most useful test
HIDA useful
Specificity improved with phenobarb 5d before scan
Duodenal aspirate
Exploratory laparotomy & intraoperative cholangiogram
ERC and MRC likely to have future
Hepatobiliary iminodiacetic acid scan

27. Ultrasound
Main utility is to r/o other extrahepatic causes (ie choledochol cyst)
Findings suggestive of biliary atresia
Absence of gallbladder
Abnormal gallbladder size and shape
“Triangular cord” sign
Absence of a common bile duct

28. Ultrasound
Fibrous triangular cord antrerior to portal vein

29. Ultrasound
Abnormally small and contracted gallbladder and irregular contour and septations in the gallbladder neck.
Common bile duct not visualized
Consistent with biliary atresia

30. Biliary Atresia Treatment Primary treatment is Kasai procedure
Early diagnosis and surgery is critical
Narrow window for optimal short and longterm outcomes
bile drainage achieved in >80% of patients <60 days of age vs. 20% of infants >90 days
4 yr survival with native liver
49% with sx <30 days of age
36% with sx at days of age
23% with sx at >90 days of age
Kasai is a portoenterostomy with roux-en-Y loop of bowel being anastomosed to the liver and portal fibrous plate

31. Kasai

32. Pearls Recognize pathologic features of jaundice
Obtain fractioned serum bili level (ie total and direct) on all 2-3 week old jaundiced infants
Infants with biliary atresia will often appear to be well in the first 1-2 weeks of life
Neonatal cholestasis is rare, but timely diagnosis is crucial!

33. References
Subcommittee on Hyperbilirubinemia. Management of Hyperbilirubinemia in the Newborn Infant 35 or More weeks of Gestation. Pediatrics. 2004;114:
Venigalla S, Gourley GR. Neonatal Cholestasis. Seminars in Perinatology.2004;28:
Suchy F. Neonatal Cholestasis. Pediatrics in Review. 2004;25:
Schreiber RA, Barker CC, Roberts EA, et al. Biliary Atresia: the Canadian Experience. Journal of Pediatrics. 2007;151:659
Abrams S, Shulman R. Causes of Neonatal Cholestasis. UpToDate. Last updated June 12, 2008.
Abrams S, Shulman R. Approach to Neonatal Cholestasis. UpToDate. Last updated September 26, 2006.

34. The End