THE JAUNDICED NEWBORN AND THE NEW AAP GUIDELINES
From the 27th Annual Las Vegas Seminars—Pediatric Update, presented by AAP California Chapters 1,2,3, and 4
M. Jeffrey Maisels, MD, Clinical Professor of Pediatrics, Wayne State University School of Medicine, Detroit, MI,
and Chairman, Department of Pediatrics, William Beaumont Hospital, Royal Oak, MI
| PART 1: WHY WORRY ABOUT JAUNDICE?
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Kernicterus in Healthy Breast-Fed Term Infants
| Introduction: jaundice occurs in almost all infants; source of aggravation to families and physicians; in rare circumstances,
can lead to kernicterus
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| Kernicterus (case): infant not feeding well after discharge; bilirubin 30 mg/dL; Crigler-Najar syndrome congenital
inability to conjugate bilirubin; retrocollis classic posture of infant in advanced stages of acute bilirubin encephalopathy;
starts with slight lethargy, slightly abnormal cry, and infant not feeding as well; tone can fluctuate; if no intervention,
infant develops classic opisthotonic posture; if no further intervention, seizures possible; in this case,
exchange transfusion futile; choreoathetoid cerebral palsy classic chronic form of bilirubin encephalopathy (paralysis
of gaze, dental dysplasia, and severe sensorineural hearing loss); these children have normal intelligence, but
bodies profoundly dysfunctional; constant movement; cannot swallow or speak well
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| Kernicterus threatens healthy newborns (Sentinel Event Alert [2001]; Joint Commission on Accreditation
of Healthcare Organizations): kernicterus—condition in newborns that leads to severely disabling
brain damage or death; results from hyperbilirubinemia; 2004 Alert—discusses American Academy of Pediatrics
(AAP) clinical practice guidelines (2004)
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| Kernicterus registry (Bhutani): 125 infants born 1979 to 2002 and discharged as “healthy”; sources of information
parents, physicians, nurses, literature, and medicolegal sources; Parents of Infants and Children with Kernicterus
(PICK) has useful website (www.pickonline.org); risk factors—two thirds of affected infants boys; nearly all
breast-fed; every infant discharged from nursery <72 hr after birth; 40% born at 35 to 38 wk gestation (near-term infants);
causes of hyperbilirubinemia—in majority, bilirubin >30 mg/dL; idiopathic (37%); hemolysis (14%); glucose-6-phosphate
dehydrogenase (G6PD) deficiency (25%; triggers include exposure to naphthalene and
Escherichia coli sepsis; almost all affected infants black); other causes (23%)
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| Kernicterus in otherwise healthy breast-fed term infants (Maisels and Newman): criteria—≥37 wk
gestation; no evidence of hemolysis, jaundice, or sepsis; no cause for elevated bilirubin other than breast-feeding; 6
cases—not one born ≥40 wk gestation; 4 of 6 at 37 wk gestation; 4 of 6 boys; presented in office or emergency department
(ED) at 4 to 10 days with bilirubin levels 39.0 to 49.7 mg/dL; conclusions—kernicterus can and does occur
in healthy breast-feeding infant if bilirubin sufficiently high
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| Cerebral palsy (CP) caused by kernicterus: incidence in Denmark 1 in 100,000 live births; probably 20 cases/
yr in United States (compared to 5000 cases of CP/yr); rare (accounts for small proportion of cases of CP); unlike
other causes of CP, kernicterus almost always preventable; ≈80% of CP caused by intrauterine events over which
physician has no control; kernicterus preventable with reasonable observation, surveillance, and adequate follow-
up
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Why Is This Happening?
| Times have changed: early discharge (infants discharged at 36 hr; before, stayed 3 or 4 days); many more mothers
breast-feeding; issue whether medical community has adapted to changes; in 1960s, ≈28% of mothers in United
States breast-fed infants at time of discharge (now, almost 70% of mothers nurse their infants); breast-feeding confers
significant health benefits (on other hand, breast-feeding associated with high bilirubin); practitioners must interpret
bilirubin level in relation to infant’s age in hours (not days) and recognize that infant leaves hospital in 36 or
48 hr
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| Natural history of jaundice in newborn: in average infant, cord blood bilirubin level ≈1.5 mg/dL; level rises
steadily to ≈8 mg/dL (on average) at 84 to 96 hr; predischarge assessment in terms of days irrelevant and misleading;
at 24.1 hr after birth, if bilirubin 8 mg/dL, infant just above 95th percentile; if bilirubin 8 mg/dL at 47.9 hr, infant
at 50th percentile (infant normal); if infant sent home from hospital at 36 to 48 hr, bilirubin level can go in only
one direction (it has not peaked yet); if physician instructs mother to return in 1 or 2 wk, he or she abandoning infant;
sooner or later, patient will develop bilirubin of 35 mg/dL or 40 mg/dL (preventable if physician sees infant
within 2 days after discharge at <72 hr
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| Visual assessment of jaundice not reliable (Davidson et al, 1941): 100 infants examined carefully every day
by experienced clinicians; visual diagnosis moderate, severe, or no jaundice, then bilirubin level used for comparison;
some infants believed markedly jaundiced had bilirubin 3 mg/dL or 4 mg/dL; more importantly, some infants
thought to have no jaundice had levels 8 to 12 mg/dL; comment—have high degree of humility in assessing jaundice;
if infant seems slightly jaundiced, obtain bilirubin or see within 2 days; difficult to see jaundice in child with
darkly pigmented skin
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| Risk factors for readmission for phototherapy (Maisels): infant born at 35 or 36 wk gestation 13 times more
likely to be readmitted for high bilirubin than at 40 wk gestation (infants 36-38 wk had ≈8 times greater risk for readmission);
other risk factors—breast-feeding; jaundice in nursery; discharge at <72 hr; perform simple risk assessment
based on, eg, epidemiologic risk factors that indicate whether infant at high risk of developing high bilirubin;
jaundice in first 24 hr; sibling that needed phototherapy; cephalhematoma or bruising caused by vacuum extraction;
blood group incompatibility; predischarge bilirubin >95th percentile
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| Breast-feeding and jaundice: breast-fed infants 3 times more likely to have bilrubin levels >12 mg/dL or >15 mg/
dL than formula-fed infants; but teaching effective breast-feeding may significantly reduce the risk for severe hyperbilirubinemia;
breast-feeding frequency in first 24 hr and likelihood of bilirubin >15 mg/dL on day 6 (study)—
if infant nursed 9 to 11 times on day 1, no risk; if infant nursed 0 to 2 times, almost 30% risk for bilirubin >13 mg/
dL; linear relationship between frequency of nursing in hospital and likelihood of infant developing high bilirubin;
to reduce risk of developing hyperbilirubinemia, help mothers breast-feed more efficiently
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| “Don’t water babies”: never supplement breast-fed infant with water if intention to lower bilirubin level; study—
breast-fed infants randomly assigned to no supplements or supplementation with dextrose water or plain water;
supplemented infants had highest bilirubin levels and unsupplemented infants had lowest bilirubin levels; have infants
nurse early and frequently
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| Diagnostic imaging: classic findings on magnetic resonance imaging (MRI) in infant with kernicterus; increased
uptake in globus pallidus bilaterally
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| PART 2: CLINICAL PRACTICE GUIDELINES
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| Why develop guidelines? to help pediatricians provide optimal care; to establish “best practice” level of care consistent
with available resources; to promote greater uniformity and consistency of care
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| AAP jaundice guidelines (10 key elements)
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 | 1) Promote and support successful breast-feeding
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| 2) Establish nursery protocols for management of jaundice; include circumstances in which nurse can order bilirubin
level without physician
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| 3) If infant jaundiced in first 24 hr, measure total serum bilirubin (TSB) or transcutaneous bilirubin (TcB)
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| 4) Recognize potential for error in visual estimation of jaundice
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| 5) Interpret bilirubin according to infant’s age in hours (not days)
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| 6) Recognize that infants born at <38 wk gestation at high risk (particularly if breast-fed)
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| 7) Perform risk assessment before discharge
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| 8) Give parents written and oral information; copy of guidelines available on AAP website (www.aap.org); also,
answers to frequently asked questions (FAQs) about hyperbilirubinemia for parents and families
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| 9) Provide appropriate follow-up based on time of discharge and risk assessment
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| 10) Treat infants, when indicated, with phototherapy or exchange transfusion
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| Risk assessment: perform on each infant; review of risk factors (prematurity, breast-feeding, early discharge, cephalhematoma,
blood group incompatibility, previous child in family with jaundice); if 4 to 6 present, infant at high
risk (if none, infant at low risk)
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| Universal screening: promoted by some experts; not difficult to get bilirubin on every infant (all get heel sticks at
24 hr after birth for metabolic screening; get bilirubin as well; cost to hospital ≈$1.50); very helpful in predicting
whether infant will develop high bilirubin; if combined with clinical risk factors, even more powerful predictor of
bilirubin; transcutaneous bilirubin meters also excellent for monitoring bilirubin levels (best to use both methods)
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| Predictive ability of a predischarge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia
in healthy term and near-term newborns (Bhutani): 3000 infants; bilirubin obtained before
discharge, at time of metabolic screen; findings—if bilirubin at birth >95th percentile, 40% likelihood of remaining
>95th percentile (bilirubin 17 mg/dL); if level <40th percentile, <1 of 1756 infants developed high bilirubin;
caveat—pattern not 100%; speaker has seen several infants who started <40th percentile and increased to >95th
percentile (levels 17 or 18 mg/dL; not 25 or 30 mg/dL)
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| Importance of gestational age (Newman): infants <38 wk gestation do not nurse as well, have livers that do not
function as well, and at greater risk for high bilirubin; looked at bilirubin levels before discharge, based on Bhutani’s
nomogram; risk of developing bilirubin >20 mg/dL—if infant starts at >95th percentile, and born at 42 wk gestation,
risk ≈5%; on other hand, 36 wk gestation and starting at >95th percentile, risk ≈42% (8-9 times greater risk; for
75th-94th percentile, similar effect); as gestational age decreases, dramatic increase in risk of developing high bilirubin
(almost no impact at lower percentile); if infant <75th or <50th percentile, gestational age does not play important
role; more risk factors—breast-feeding; sibling with jaundice; jaundice in first day of life; combined with
gestational age, powerful predictors of likelihood of high bilirubin level
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| Provide appropriate follow-up: according to time of discharge and risk factors; reasonable options if physician
unable to follow up—home nurse visit; examination in after-hours clinic; outpatient TSB or TcB
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| Tools for risk assessment at bedside: low-tech—eg, wallet-sized nomogram and risk factors for developing
high bilirubin level; phototherapy guidelines; exchange transfusion guidelines; high-tech—having hospital laboratory
provide infant’s age, percentile, and management protocol; computerized charts; flow sheet in nursery—
nomogram; charting bilirubin levels (serum or transcutaneous); infant’s age in hours; time of measurement; major
and minor risk factors of developing high bilirubin; factors that decrease risk of developing high bilirubin; if seeing
infant Monday after Thursday, document fact in chart and why; take-home message—any infant discharged at <72
hr should be seen within 2 days of discharge; www.BiliTool.org—very useful and user-friendly mechanism for following
bilirubin levels
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| More about follow-up: worth repeating—if infant discharged <72 hr after birth, physician or nurse needs to see
infant within 2 days of discharge; home nursing visits within 48 hr of discharge (Paul)—with home visits by nurse,
number of infants readmitted with jaundice or dehydration reduced from 2.8% to 0.6%; average cost per child after
nursery discharge lower for families that had home visit from nurse than families of children readmitted to hospital;
if many risk factors present, see patient earlier (if few risk factors, see later, but document reasoning in chart); if pediatricians
provide appropriate follow-up, patients will not get into trouble
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| If very jaundiced infant presents in office (bilirubin level 25 mg/dL or 28 mg/dL): do not send patient to
ED (not equipped for phototherapy); avoid unnecessary septic work-up; ≈6 or 7 hr later, when results back and triage
finished, infant admitted to pediatric floor (bilirubin may have increased to 35 mg/dL); if need to admit jaundiced
infant, send directly to pediatric floor, start phototherapy, get bilirubin level, prepare for possible exchange
transfusion
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Educational Objectives
| The goal of this program is to educate the listener about jaundice in the newborn. After hearing and assimilating this
program, the clinician will be better able to:
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| 1. Recognize the risk for kernicterus in healthy breast-fed term infants.
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| 2. Describe risk factors for severe hyperbilirubinemia.
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| 3. Perform predischarge risk assessment for jaundice on an individualized basis.
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| 4. Describe current jaundice guidelines from the American Academy of Pediatrics.
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| 5. Perform appropriate follow-up after discharge.
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Predischarge Assesment for the Risk of Hyperbilirubinemia in Infants ≥35wk Gestation (Pediatrics
2004; 114:297-316)
Date
| Title
| Age (hr)
| TcB
| TSB
| Intials
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|---|
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|
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TcB–Transcutaneous Bilirubin
TSB–Total Serum Bilirubin/Direct
Risk Factors for Development of Severe Hyperbilirubinemia (Pediatrics 2004; 114:297-316)*
Risk Factors
| Major Risk
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| Minor Risk
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| Decreased Risk
|
|
|---|
Predischarge TSB or TcB
(see nomogram above)
| In high risk zone (>95%)
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| In high inermediate risk zone
(>75%)
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| Low risk zone (<40%)
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| Visible jaundice
| First 24 hr
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| Before discharge
|
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| Gestational age
| 35-36 wk
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| 37-38 wk
|
|
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| Previous sibling
| Received phototherapy
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| Jaundiced, no phototherapy
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| ≥41 wk
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| Blood groups
hemolytic disease
| Blood grp incompatibility with
+DAT. Other known hemolytic
disease (eg G6PD deficiency)
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| Feeding
| Exclusive breast (risk if poor
feeder or wt. loss)
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| Breast fed, nursing well
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| Exclusive formula feeding
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| Race
| East Asian
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| Hispanic (Mexican)?
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| African American *unless
G6PD def.
≈12% are G6PD deficient
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| Other factors
| Cephalhematoma or significant
bruising
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| Macrosomic infant of IDM, male
gender, maternal age ≥25 yr
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| Discharged from hospital
after 72 hr
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*The more risk factors present, the greater the risk of developing severe hyperbilirubinemia
Resources
www.pickonline.org; www.aap.org; www.BiliTool.org
Suggested Reading
American Academy of Pediatrics Subcommittee on Hyperbilirubinemia: Management of hyperbilirubinemia
in the newborn infant 35 or more weeks of gestation. Pediatrics 114:297, 2004; Bhutani VK et al: Predictive
ability of a predischarge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy-
term and near-term newborns. Pediatrics 103:6, 1999; Bhutani VK et al: Risk management of severe neonatal hyperbilirubinemia
to prevent kernicterus. Clin Perinatol 32:125, 2005; Bhutani VK: Combining clinical risk factors
with serum bilirubin levels to predict hyperbilirubinemia in newborns. J Pediatr 147:123, 2005; Huang M-J et al:
Risk factors for severe hyperbilirubinemia in neonates. Pediatr Res 56:682, 2004; Ip S et al: An evidence-based review
of important issues concerning neonatal hyperbilirubinemia. Pediatrics 114:e130, 2004; Maisels MJ, Kring
E: Transcutaneous bilirubin levels in the first 96 hours in a normal newborn population of > or = 35 weeks’ gestation.
Pediatrics 117:1169, 2006; Maisels MJ, Watchko JF: Treatment of jaundice in low birthweight infants.
Arch Dis Child Fetal Neonatal Ed 88:F459, 2003; McDonagh AF, Maisels MJ: Bilirubin unbound: déjà vu all
over again? Pediatrics 117:523, 2006; Newman TB et al: Combining clinical risk factors with bilirubin levels to
predict hyperbilirubinemia in newborns. Arch Pediatr Adolesc Med 159:113, 2005; Newman TB, Maisels MJ:
How to avoid kernicterus. J Pediatr 142:212, 2003; Palmer RH et al: Hyperbilirubinemia in benchmarking. Pediatrics
114:902, 2004; Watchko JF, Maisels MJ: Jaundice in low birthweight infants: pathobiology and outcome.
Arch Dis Child Fetal Neonatal Ed 88:F455, 2003.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. For this issue,
the faculty reported nothing to disclose.
Dr. Maisels was recorded at the 27th Annual Las Vegas Seminars—Pediatric Update, presented November 17-20,
2005, in Las Vegas, NV, by AAP California Chapters 1,2,3, and 4. The Audio-Digest Foundation thanks Dr. Maisels
and the sponsors for their cooperation in the production of this program.
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