5History Pregnancy Delivery Mother was 23 yo Caucasian female G1P0 O negRoutine serology was normalGBS negativeNonsmoker. No EtOHUncomplicated pregnancy (no PIH or GDM)Delivery39wks GAROM x 3 hrsBW=3220Apgar 91,95DAT negativeNewborn metabolic screen was normalTbili at discharge =190d/c home 24hrs postpartumConsider pointing out tbili on nomogram
6History Followed by GP qweekly x 6 wks Jaundiced noted again at 6wk follow up with maternity care clinic1 oz wt loss in past monthExclusively 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
9Labs/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 – NORMALUrinalysis/R&MLARGE Leuks,SMALL blood20-30 WBC/hpf0-5 RBCFew bacteriaLFT/enzymesTbili 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 38INR 1.1PTT 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
10Objectives Review features of physiologic and pathologic jaundice Review approach to neonatal cholestasisHighlight some common pitfallsReturn to the case to review the work up and diagnosis
11HyperbilirubinemiaHas increasingly become a presenting complaint to ER due to early postpartum dischargeHowever, still rare to encounter in Calgary ERScreened by PHN/GP in first 3-5 days postpartumDirect admit to PLC Unit 31 for assessment +/- phototherapyVery 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.
13Physiologic vs. Pathologic Jaundice in the Newborn
14Physiologic vs. Pathologic Jaundice in the Newborn1 Unconjugated hyperbilirubinmia60% term & >80% preterm neonates in first weekRises at rate <85 umol/L/dayAppears on 2nd or 3rd day of lifeTypically peaks btwn days 2-4Begins to decline on days 5-7 at rate of 34 umol/L/dayPathologicAppears <24 hrsExcessive for infant’s age (Tbili > 205 umol/L)Elevated direct bilirubinJaundice present at or beyond 3 wksSick infantTbili rising >85 umol/L/dayUnexplained jaundice following phototherapyJaundice in the presence of risk factorsCover 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 jaundiceThis 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.
16Ddx of Hyperbilirubinemia According to Time of Onset First 24 hours24-72 hours72-96 hours> 1 weekOften pathologicHemolysis (Rhor ABO)Sepsis (GBS,TORCH)CephalohematomaSpherocytosisHemorrhagicdisease of thenewbornOften pathologicBreast milk jaundiceProlongedPhysiologicHypothyroidismNeonatalHepatitisGalactosemiaFamilialCholestasisBiliary atresiaPaucity of bileductsPhysiologicPolycythemiaDehydrationHemolysisG6PDPK defCephalohematomaSpherocytosisSepsis/TORCHPhysiologicDehydrationSepsisGilbert’sCrigler-NajjarHypoxia/respdistress/hypoG
17Neonatal CholestasisDefined as the impaired canalicular biliary flow resulting in acumulation of biliary substances (bilirubin, bile acids, and cholesterol)2Estimated incidence of 1/2500 live birthsJaundice at 2-3 weeks of age increases suspicion22.4-15% of newborns are jaundice at 2 weeks of age6Estimated that jaundiced infants at 2 weeks of age would need to be tested to detect one case of cholestasis 26
18Common Pitfalls Breast feeding jaundice Breast milk jaundice Exaggeration of physiologic jaundiceDay 2 7Premature babies: can last up to 10 daysBreast milk jaundice2% of breast fed babiesStarts ~ day 7, persists until week 2-3May persist for 3-10 weeks at low levelsUnconjugatedTheory: glucuronidase in breast milk increased enterohepatic bilirubin re-circulation
19Neonatal Cholestasis Clinical Presentation Prolonged jaundice Pale stoolsDark urineCoagulopathyHepatomegalySplenomegalyRUQ massFTTLess specific suggestive of underlyingmetabolic, CNS, or infectious aetiology:FeverIrritabilityLethargy,SeizuresPoor feedingDysmorphic features
21Approach to Neonatal Cholestasis Initial investigations: Establish cholestasis and determine severity of diseaseDetailed hx, examFractioned serum biliTests for liver injury (AST, ALT, ALP, GGT)LFT (Albumin, INR, PTT, serum ammonia, glucose)Detect conditions that require immediate treatmentCBC, blood & urine cultures to r/o sepsisSerum T4 and TSHMetabolic Screen: lactate, ammonia, iron, ferritin, urinalysis, urine amino acids and organic acidsViral serologies, VDRL, and cultures
22Approach to Neonatal Cholestasis Differentiate extrahepatic disorders from intrahepatic causes of cholestasisU/SHepatobiliary scintigraphyPerc liver bx,Exploratory laparotomy with intraoperativeEstablish other specific diagnosisα-1-antitrypsin, CF, Alagille, PFIC, storage disorders
23Back to the Case Initial investigation: establish cholestasis Detect conditions that require treatmentDifferentiate extrahepatic disorders from intrahepatic causes of cholestasisInvestigate for the rare diagnosis
24BiliaryAtresiaInflammation of bile ducts leading to progressive obliteration of the extrahepatic biliary tractMost common cause of cholestasis in the first few weeks of lifeIncidence of 1/10,000 to 1/20,000 birthsCause remains unknown though various infectious (CMV, reovirus, rotavirus) and genetic causes have been proposed
25Biliary Atresia Jaundice typically develops in weeks 3-6 Uncommon for jaundice to be present at birth10-15% association with congenital malformations (polysplenia, malrotation, etc)
26Biliary Atresia Diagnosis U/S can be suggestive Liver biopsy is the most useful testHIDA usefulSpecificity improved with phenobarb 5d before scanDuodenal aspirateExploratory laparotomy & intraoperative cholangiogramERC and MRC likely to have futureHepatobiliary iminodiacetic acid scan
27UltrasoundMain utility is to r/o other extrahepatic causes (ie choledochol cyst)Findings suggestive of biliary atresiaAbsence of gallbladderAbnormal gallbladder size and shape“Triangular cord” signAbsence of a common bile duct
28UltrasoundFibrous triangular cord antrerior to portal vein
29UltrasoundAbnormally small and contracted gallbladder and irregular contour and septations in the gallbladder neck.Common bile duct not visualizedConsistent with biliary atresia
30Biliary Atresia Treatment Primary treatment is Kasai procedure Early diagnosis and surgery is criticalNarrow window for optimal short and longterm outcomesbile drainage achieved in >80% of patients <60 days of age vs. 20% of infants >90 days4 yr survival with native liver49% with sx <30 days of age36% with sx at days of age23% with sx at >90 days of ageKasai is a portoenterostomy with roux-en-Y loop of bowel being anastomosed to the liver and portal fibrous plate
32Pearls Recognize pathologic features of jaundice Obtain fractioned serum bili level (ie total and direct) on all 2-3 week old jaundiced infantsInfants with biliary atresia will often appear to be well in the first 1-2 weeks of lifeNeonatal cholestasis is rare, but timely diagnosis is crucial!
33ReferencesSubcommittee 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;151:659Abrams 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.