JAUNDICE AND THE NEWBORN Abbey Rupe, MD

Objectives Definitions Prevention Risk factors Assessment Treatment

What is jaundice? Hyperbilirubinemia Indirect/Unconjugated Direct/Conjugated Considered elevated if direct portion is >20% of total bilirubin level Scope won’t be discussed in this lecture

Definitions Unconjugated Physiologic jaundice Breast-feeding jaundice Most babies develop some jaundice Mean peak of 5-6 mg/dl between 60-72 hr of life Breast-feeding jaundice Decreased calories, increased enterohepatic circulation Breast-milk jaundice Prolonged after 2-3 weeks of age ?? Protein in breast milk that increases enterohepatic circulation Peak and age range differs between races

Definitions Pathologic Jaundice appearing in first 24 h of life TSB > 95th percentile for age TSB increasing at rate >0.2 mg/dl/h or > 5 mg/dl/d Elevated direct component Jaundice persisting > 2 weeks in full-term infants Exception: breast-milk jaundice “Severe” hyperbilirubinemia Generally considered to be TB >25-30

Complications of untreated jaundice Bilirubin-induced neurologic dysfunction (BIND) Bilirubin crosses BBB and binds to brain tissue Risk increased when TB >25-30 Acute bilirubin encephalopathy (ABE) Initial phase: lethargy, hypotonia, decreased movement, poor suck Intermediate phase: stupor, irritability, increased tone (retrocolis and opisthotonos), fever Advanced phase: deep stupor or coma, inability to feed, shrill cry, apnea, seizures **potentially reversible! Unconjugated bili can cross BBB and penetrate brain cells, may lead to neuronal dysfunction and death

Complications Chronic bilirubin encephalopathy (kernicterus) Choreoathethoid cerebral palsy Sensorineural hearing loss Palsy of vertical gaze Dental enamel hypoplasia Up to 10% mortality Most (but no all) infants with kernicterus previously manifested symptoms of ABE

Why do neonates become jaundiced? Increased bilirubin production More RBCs + shorter RBC life span = increased turnover and increased bilirubin Decreased bilirubin clearance Deficiency of UGT UGT activity at 7 days of age is approx 1% of adult Reaches adult levels around 14 days of age Increased enterohepatic circulation UGT: uridine diphosphogluconurate glucuronosyltranferase

Pathologic jaundice--causes Rh or ABO incompatibility Enzyme deficiencies: G6PD, pyruvate kinase Hemoglobinopathies Infection Increased RBC load Cephalohematomas, etc Polycythemia Infants of diabetic mothers

Pathologic jaundice--causes Disorders of bilirubin clearance Crigler-Najjar, Gilbert Metabolic and endocrine Galactosemia, hypothyroidism Increased enterohepatic circulation Breast-feeding jaundice Conditions causing GI obstruction or decreased motility

Risk factors for severe jaundice Major: Predischarge bili in high-risk zone Observed jaundice in 1st 24 hours of life Blood group incompatibility w/ positive DAT Previous sibling required ptx Cephalotematoma or other significant bruising Exclusive breastfeeding (esp if not going well and weight loss is excessive) East Asian race (again, this is infants 35 weeks and older

Risk factors for severe jaundice Minor risk factors Predischarge bili in high-intermediate risk zone GA 37-38 weeks Jaundice observed before discharge Previous sibling with jaundice Macrosomic IDM Maternal age ≥ 25 years Male gender

Risk factors for severe jaundice DECREASED risk Pre-discharge bili in low-risk zone GA ≥ 41 weeks Exclusive bottle feeding Black race Discharge from hospital after 72 hours

Hyperbilirubinemia--prevention Pregnant women: ABO and Rh testing Rhogam as indicated screen for isoimmune antibodies If mom is Rh- or ABO/Rh status unknown Check blood type, Rh, and DAT on neonate (cord blood) If DAT positive: needs frequent (q6-12hr) checking of TSB Most of these are standing orders

Jaundice--prevention Newborn nursery: Advise mothers to nurse 8-12 times per day for first several days Evaluate for jaundice every time vitals taken (q8-12 hr)

Testing for jaundice Before discharge, ALL newborns should be assessed for jaundice (2004 AAP Practice Guideline) Visual assessment Need adequate ambient light or daylight fluorescent light Subjective and not recommended as lone assessment More difficult in darker-complected infants TSB (total serum bilirubin) Oftentimes drawn with metabolic screen TcB (transcutaneous bilirubin) Method implemented at SRHC in 2010

Assessment tools AAP bilirubin nomograms Electronically UpToDate calculator BiliTool.org Online calculator App for iPhone or iPod touch Palm OS

Phototherapy

Using the nomograms Use total bilirubin (don’t subtract direct component) Risk factors: Isoimmune hemolytic disease G6PD deficiency Asphyxia Significant lethargy Temp instability Sepsis Acidosis Albumin < 3.0 (if measured)

Exchange transfusion

Discharge and follow-up Infant Discharged Should Be Seen By Age Before age 24 hours old 72 hours old Between 24 and 47.9 h 96 h Between 48 and 72 h 120 h Follow-up by a “qualified health care professional” typically with PCP or mid-level provider nurse/lactation specialist home health nurse visit If follow-up cannot be ensured, may be necessary to delay discharge “qualified” implies that, if nurse or HH visit, they have been trained to assess for jaundice and the ability to change to a MD visit if needed (HH nurse when WMC did visits had a biliometer)

Anticipatory Guidance Jaundice progresses head to toe, then as it resolves, disappears from toe to head Testing for jaundice: blanch skin with finger Call if: Jaundiced to belly button Not waking well for feeds or feeding poorly Decreased wet diapers Shrill cry

Follow-up appointment Weight and % change from BW Adequacy of po intake Pattern of voiding and stooling Presence or absence of jaundice +/- checking bili level If predischarge bili was high-intermediate risk, I nearly always recheck a bili If predischarge bili was low-risk, I rarely do If predischarge bili was low-intermediate, I do if concerns present

So . .. .you’ve reached LL. Now what? History and physical exam Laboratory testing Phototherapy Assess hydration

Laboratory evaluation Approaching or at light level: Direct and total bilirubin Blood type and DAT CBC Peripheral smear Consider: retic count, G6PD, ETCOc Consider: UA (for reducing substances) with culture, sepsis eval

Lab evaluation Approaching exchange levels or not responding to phototherapy Retic, G6PD, albumin, ETCOc UA Sepsis eval Elevated direct (or conjugated) bilirubin UA and urine culture Evaluate for sepsis if indicated by history and physical exam

Treatment—Phototherapy Mechanism of action: Exposes skin to light of specific wavelength (425-475 nm/blue-green spectrum) Converts bilirubin to lumirubin Lumirubin is more soluble than bilirubin and is excreted without conjugation into the bile and urine

Phototherapy options Bili blanket Bili bed “Bank” phototherapy Home or hospital Bili bed “Bank” phototherapy Hospital only Home vs hospital Home is an option 2-3mg/dl below LL in infant with no risk factors and caregivers with ready access to medical care

Treatment--phototherapy Technique—bank phototherapy Infant should wear diaper only, and diaper should be pulled down as much as possible to increase skin exposure “baby sunglasses” Ensure that banks of lights are at appropriate distance from infant Infant needs to remain under lights continuously, only to be taken out for feedings Can utilize biliblanket to continue some ptx during feeds

Phototherapy phototherapy typically results in a decline of TB of 2-3 mg/dl within 4-6 hours Obviously, more lights = faster decline Recheck TB within 2-6 hours of starting ptx Then, recheck every 6-12 hours, if TB is falling If doing home therapy, need to redraw daily Hospitalize if surpasses LL, excessive rate of rise, or other concerns develop

Phototherapy—side effects Generally considered safe Transient erythematous rashes Loose stools Hyperthermia Increased insensible water loss Possible retinal degeneration (hence the sunglasses) Parents/caregivers: some models can cause HA and nausea Frustrating to not get to hold baby “bronze baby syndrome” If used on infant with cholestasis

Management—assess hydration Maintaining adequate hydration and UOP is important Lumirubin excreted in urine > stool Encourage breast or bottle feeding Lactation consult prn Supplement with EBM or formula in breastfed infants with excessive weight loss (>12%) or evidence of hypovolemia IVF if oral intake is inadequate ***suppositories

Phototherapy . .. When to stop? No strict guideline when TSB <13-14 When TSB back to, or lower-than, level at which ptx was initiated Sometimes at lower level if started during NB stay and treatment initiated at lower LL

Phototherapy . . . When to stop? “checking for rebound” TB will typically re-increase by small amount (typically <1 mg/dl) after discontinuation of ptx DON’T have to keep pt hospitalized to check for rebound, unless risk-factors present DO check in hospital or clinic the next day if: ptx discontinued prior to 5-6 days old (may not have reached peak yet) Other concerns For “nervous Nellie’s” (like myself): night before anticipated discharge, check TSB. Continue ptx until 2 or 3am, then d/c. Check bili with AM labs, should see if significant rebound present

If not improving Likely that hemolysis is occurring: Increase # banks Labs: Retic, G6PD, albumin, ETCOc Sepsis eval UA and urine culture Add IVF Consult pediatrician +/- neonatologist Exchange transfusion in NICU

Lab evaluation Jaundice preset at ≥ 2-3 weeks Total and direct bili If direct bili elevated, evaluate for causes of cholestasis Check NB thyroid and galactosemia; evaluate infant for signs/sx of hypothyroidism If indirect elevated and breast-fed, potentially breast-milk jaundice Option to give formula in place of breast milk x24 hours (controversial)

?Sunny window? Technically. . .. NO Risk for sunburn Risk for hypo- or hyper-thermia