Jaundice in the Healthy Term Infant

British Columbia Reproductive Care Program
Newborn Guideline 4
JAUNDICE IN THE HEALTHY TERM NEWBORN
INTRODUCTION
During the first week of life, all newborns have increased bilirubin levels by adult standards, with
approximately 50% of term infants having visible jaundice. Despite progress in neonatal care and the
virtual absence of classic bilirubin encephalopathy, safe bilirubin levels have not been established with
absolute certainty. There has been an increase in the number of term infants reported with
kernicterus1,2 and the number of readmissions to hospital for jaundice has increased in recent years3.
This has been attributed to shorter length of postpartum hospital stays without comprehensive followup4,5.
When carefully reviewed, the data from numerous studies of bilirubin toxicity are so complex that it is
difficult to derive a single rational approach to jaundiced neonates6. One principle is well accepted: if
there is any evidence that a neonate’s jaundice is not physiologic, the cause should be investigated
prior to the initiation of treatment6.
SIGNIFICANCE
Neonatal Jaundice is of concern due to:
•
•
The risk of bilirubin encephalopathy/kernicturus
The possibility that the jaundice may be a sign of a serious underlying illness
RISK FACTORS 7
•
•
•
•
•
•
•
•
•
•
•
family history of newborn jaundice (especially sibling), anemia, liver disease, or inborn errors of
metabolism
plethora, polycythemia, bruising, cephahematoma
poor feeding, vomiting, delayed passage of meconium
excessive weight loss
sepsis
asphyxia
relative prematurity or small for gestational age
hypothyroidism, hypopituitarism
certain ethnic groups i.e. East Asian, Native American
infant of a diabetic mother
maternal ingestion of sulfonamides or antimalarial drugs
April 1993 – Original
February 1994 - Revised
April 2002 - Revised
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Jaundice in the Healthy Term Newborn
CAUSES
I.
PHYSIOLOGIC JAUNDICE
Increased bilirubin load due to:
•
•
•
•
•
Increased red blood cell volume
Immaturity of bilirubin conjugation in the liver at birth
Increased enterohepatic circulation of bilirubin
Decreased red blood cell survival
Decreased uptake of bilirubin from the plasma by the liver
II. INCREASED BREAKDOWN OF RED BLOOD CELLS
•
•
•
•
•
•
Blood group and Rh incompatibility
Red blood cell defects (G6PD deficiency, spherocytosis)
Rare blood group incompatibilities
Polycythemia
Sequestered blood (bruising, hematoma)
Infection
III. DECREASED CONJUGATION OF BILIRUBIN
•
•
Prematurity
Rare inherited defects
IV. INCREASED REABSORPTION OF BILIRUBIN FROM THE GI TRACT
•
•
•
•
Asphyxia
Delayed feedings
Bowel obstruction
Delayed passage of meconium
V. IMPAIRMENT OF BILE EXCRETION
•
•
•
•
•
•
Sepsis
Intrauterine infections
Hepatitis
Cholestatic syndromes
Biliary atresia
Cystic fibrosis
VI. BREAST MILK JAUNDICE
The association between breastfeeding and higher bilirubin levels is well established, however the
cause for this has not been determined with certainty6.
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Jaundice in the Healthy Term Newborn
A.
Early Breastfeeding Jaundice
• Develops within 2 to 4 days of birth
• Most likely related to infrequent breastfeeding with a limited fluid intake
• May be related to increased reabsorption of bilirubin from the bowel
B. Late Breast Milk Jaundice
• Much less common
• Develops 4 to 7 days after birth, peaks day 7 to 15
• Cause remains unknown despite numerous theories and studies.
STRATEGIES TO DECREASE INCIDENCE
I. LABOR AND DELIVERY
•
avoid trauma during labor and delivery8
II. BREASTFEEDING
•
•
•
•
•
provide early assistance, education and support for breastfeeding
ensure parental education regarding signs of adequate hydration, signs of jaundice and feeding1
initiate early and frequent feedings – at least 8 feeds in 24 hours6,8. Avoid separation of mother
and baby.
encourage the ingestion of colostrum to increase stooling which prevents reabsorption of bilirubin
supplementation with water does not affect bilirubin levels and is not recommended. If
supplementation is necessary due to inadequate intake, the mother should pump her breasts and
give expressed breastmilk and/or formula rather than water.
III. DISCHARGE/FOLLOW-UP
•
•
•
ensure adherence to evidence-based and current postpartum discharge criteria9
initiate early postpartum follow-up once discharged from hospital. All infants discharged prior to
48 hours of age should be evaluated by a health care professional within 48 hours after discharge6,9
ensure community mechanisms for follow-up and referral between health care providers (See
example in Appendix 1: Management of Newborn Jaundice at Home Program)
SCREENING
I. TRANSCUTANEOUS
Use of an icterometer or transcutaneous jaundice meter is sometimes used as a screening device in
healthy term infants8,10. Accuracy may be limited by the changing pigmentation of the skin, the
duration of jaundice and the effect of phototherapy11.
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Jaundice in the Healthy Term Newborn
II. BILIRUBIN MEASUREMENT
Several studies have looked at the predictive ability of predischarge serum bilirubin testing12,13,14. To
date, routine bilirubin investigation for healthy term newborns is not indicated. However, if the
infant’s level of jaundice is a concern at discharge, it may be prudent and helpful to obtain a bilirubin
level at the time that the PKU specimen is collected. Reference to the Bhutani Graph (Appendix 3,
page 17) may then help to determine whether further bilirubin levels should be obtained.
ASSESSMENT
I. COLOUR
Kramer15 described the cephalocaudal progression of jaundice in term infants. He drew attention to
the observation that jaundice starts on the head, and extends towards the feet as the level rises. This is
useful in deciding whether or not a baby needs to have the serum bilirubin (SBR) measured. Kramer
divided the infant into 5 zones. The SBR range associated with progression to the zones is as follows:
Zone
SBR
(umol/L)
1
100
2
150
3
200
4
250
5
>250
Adapted from the Department of Neonatal Medicine Protocol Book, Royal Prince
Alfred Hospital, University of Sydney, Australia, 199816
The colour of the skin should be evaluated after the skin has
been blanched by pressure from the thumb in a well lit room
(or natural daylight if in the home).
II. AGE
Jaundice before 24 hours of age is always pathological.
III. FEEDING BEHAVIOUR
•
•
•
as bilirubin levels rise, the baby may become more lethargic
after the first 1-2 days of life, newborns should breastfeed at least 8 times in 24 hours
if baby is sleepy during feeds, utilize waking techniques
IV. HYDRATION
Adequate intake can be determined by the baby’s:
• Skin turgor
• Moistness of mouth
• Weight
• Energy levels
• Feeding pattern/behavior
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Jaundice in the Healthy Term Newborn
•
Elimination (See guide below)
Guide for Healthy Term Newborn Output
Day
1
2
3
4
5
Number of Stools/24 hours
at least one meconium
at least one meconium
at least 1 transitional
at least 2 + yellow/seedy
at least 2 + yellow/seedy
Number of Wet diapers/24 hours
at least 1
at least 2
at least 3
at least 4
5-6
See BCRCP British Columbia Newborn Care Path: Outcomes, Teaching & Interventions document for norms27.
V. OTHER ILLNESS
In association with other findings, jaundice may be a sign of serious illness. Each jaundiced infant
should be assessed to see whether the following danger signs are present:
•
•
•
•
•
•
•
•
•
•
Family history of significant hemolytic disease
Onset of jaundice within 24 hours
Pallor, bruising, petechiae
Lethargy
Poor feeding
Fever
Vomiting
Dark urine and light stools
Hepatosplenomegaly
High pitched cry
CLINICAL MANAGEMENT
Clinical management is aimed at avoiding bilirubin encephalopathy with it’s long term neurological
complications. Adequate hydration is an important consideration in the infant with moderate to high
bilirubin levels.
Fundamental to management is a good history and physical examination, together with appropriate
investigations including:
•
•
•
•
Unconjugated and conjugated bilirubin
Blood group determination with a direct antibody test (Coomb’s test)
Hemoglobin and hematocrit
Other lab investigations (e.g. T4, G6PD) may be required depending on the patient assessment1
Once the serum bilirubin reaches “risk” levels,1,12,17 the standard treatment is the use of phototherapy
and/or exchange transfusion. Several expert bodies have developed guidelines to assist care providers
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Jaundice in the Healthy Term Newborn
determine the appropriate time to implement each therapy as well as how to provide the therapy most
effectively.1,12,17
The most common guidelines utilized in risk identification and management of hyperbilirubinemia are
listed below.
Appendix 2: Approach to the management of hyperbilirubinemia in term newborn infants1.
A Joint Statement: Canadian Paediatric Society & College of Family
Physicians of Canada (February 2001)
Appendix 3: Hyperbilirubinembia risk designation for term and near-term well
newborns12.
Bhutani at al, (1999) Pediatrics Vol 103, No. 1, p6-12.
Appendix 4: Management of hyperbilirubinemia in healthy term newborns17.
American Academy of Pediatrics (1994)
OTHER ISSUES IN THE MANAGEMENT OF JAUNDICE
I. BREASTFEEDING AND PHOTOTHERAPY
•
•
•
•
Interruption of breastfeeding is usually not indicated6.
An adequate intake of milk minimizes the bilirubin level by stimulating bowel emptying.
Encourage frequent and effective breastfeeding (as least 8X in 24 hours)6,18
Breastfeeding may be interrupted for diagnostic or therapeutic purposes when the bilirubin is high
and there is the risk of an exchange transfusion. Should this occur:
• continue phototherapy
• consider discontinuing breastfeeding for 24 hours, or
• alternate breastfeeding with formula feeding if fluid intake is of concern
• offer positive support for breastfeeding. Encourage maintenance of lactation by using a breast
pump or manual expression during the period of interrupted breastfeeding6.
Glucose water will not reduce serum bilirubin levels and may interfere with breastfeeding6.
II. DAYLIGHT TREATMENT
Exposing infants to indirect sunlight via a window to decrease bilirubin levels has been a long
standing practice19. Controlled studies on this treatment have not been done. Mild jaundice requires
no sunlight exposure, as it sends a false note to parents that their baby has a significant problem when
in fact (s)he has not. If an infant has jaundice that needs treatment according to accepted guidelines,
then it should be investigated further.
III. FIBROPTIC PHOTOTHERAPY
Use of fibroptic or “bili blankets” is gaining increased interest. A Cochrane Database Review20 found
that fibroptic phototherapy was more effective at lowering serum bilirubin than no treatment, but less
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Jaundice in the Healthy Term Newborn
effective than conventional phototherapy. A combination of fibroptic and conventional phototherapy
was more effective than conventional phototherapy alone. No conclusion could be made on the
superiority of one fibroptic device over another. No trials have been identified which support the view
that fibroptic devices interfere less with infant care or impact less on parent-child bonding.
At this time, “bili blankets” should not be used alone to treat non-physiologic causes of jaundice or
those infants at risk of requiring an exchange transfusion.
IV. HOME PHOTOTHERAPY
There are few articles in the literature which address this issue.21-24 With the advent of fibroptic
blankets and portable bilibeds, home phototherapy has been implemented in a few communities
throughout Canada.25-27 To date, there are no published evidence-based guidelines on the use of home
phototherapy.
CLINICAL INDICATORS FOR EVALUATION
•
•
•
Serum bilirubin levels at which phototherapy is initiated (age specific in hours of life).
Bilirubin levels at which the infant is readmitted.
Numbers of readmissions for jaundice.
REFERENCES
1. Canadian Paediatric Society & the College of Family Physicians of Canada. (1999). Approach to
the management of hyperbilirubinemia in term newborn infants. Paediatrics and Child Health, 4(2),
161-164. Access from: www.cps.ca/english/statements/FN/fn98-02.htm.
2. Maisels, J. & Newman, T. (1998). Jaundice in full-term and near-term babies who leave the
hospital within 36 hours. Clinics in Perinatology, 25(2), 295-302.
3. Maisels, J. & Kring, E. (1998). Length of stay, jaundice and hospital readmission. Pediatrics,
101(6), 995-998.
4. Gurpp-Phelan, J., Taylor, J., Liu, L. & Davis, R. (1999). Early newborn hospital discharge and
readmission for mild and severe jaundice. Archive of Pediatric and Adolescent Medicine, 153, 12831288).
5. Liu, S., Wen, S., McMillan, D., Trouton, K., Fowler, D. & McCourt, C. (2000). Increased
neonatal readmission rate associated with decreased length of hospital stay at birth in Canada.
Canadian Journal of Public Health, 91(1), 46-50.
6. American Academy of Pediatrics & American College of Obstetricians and Gynecologists.
(1997). Guidelines for Perinatal Care (4rd Edition). American College of Obstetricians and
Gynecologists, Elk Grove Village, IL: American Academy of Pediatrics. Washington, DC.
7. Banks, J., Montgomer, D., Coody, D & Yetman, R. (1996). Hyperbilirubinemia in the term
newborn. Journal of Pediatric Health Care, 10(5), 228-230.
April 2002
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Jaundice in the Healthy Term Newborn
8. Blackburn S. (1995). Hyperbilirubinemia and neonatal jaundice. Neonatal Network, 14: (7);15-24.
9. Canadian Paediatric Society & the Society of Obstetricians and Gynaecologists of Canada. (1996).
Joint Policy Statement: Facilitating discharge home following a normal term birth. Paediatric & Child
Health,1(2), 165-168.Access from: http://www.cps.ca/english/statements/FN/fn96-02.htm.
10. Bhutani V, Gourley G, Adler S, Kreamer B, Dalin C, Johnson L. (2000). Noninvasive
Measurement of Total Bilirubin in a Multiracial Predischarge Newborn Population to Assess the Risk
of Severe Hyperbilirubinemia. Pediatrics (106), NO 2: Part 1 of 3.
11. Schwoebel, A. & Sakraida. (1997). Hyperbilirubinemia: New approaches to an old problem.
Journal of Perinatal and Neonatal Nursing, 11(3), 78-97.
12. Bhutani, V., Johnson, L. & Sivieri, E. (1999). Predictive ability of a predischarge hour-specific
serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns.
Pediatrics, 103(1), 6-14.
13. Seidman, D., Ergaz, Z., Paz, I., Laor, A., Revel-Vilk, S., Stevenson, D. & Gale, R. (1999).
Predicting the risk of jaundice in fullterm healthy newborns: A prospective population-based study.
Journal of Perinatology, 19(8), 564-567.
14. Alpay, F., Sarici, U., Tosuncuk, D., Serdar, M., Inanc, N. & Gokcay, E. (2000). The value of
first-day bilirubin measurement in predicting the development of significant hyperbilirubinemia in
health term newborns. Pediatrics, 106(2).
15. Kramer L. 1969. Advancement of dermal icterus in the jaundiced newborn. American Journal of
Diseases in Children, 118, 454-458.
16. Royal Prince Alfred Hospital. 1998. The department of neonatal medicine protocol book:
jaundice. Sydney: Author. Accessed May 2001 from
www.cs.nsw.gov.au/rpa/neonatal/html/newprot/jaund2.htm.
17. American Academy of Pediatrics. (1994). Practice parameter: Management of
hyperbilirubinemia in the healthy term newborn. Pediatrics, 94(4), 558-565)
http://www.aap.org/policy/hyperb.htm
18. International Lactation Consultant Association. (1999). Evidence-Based Guidelines for
Breastfeeding Management During the First Fourteen Days. Raleigh, NC: Author.
19. Mohrbacher, N. & Stock, J. (1997). The Breastfeeding Answer Book. Illinois: La Leche League.
20. Mills, J. & Tudehope, D. (2001). The Cochrane Database of Systemic Reviews: Fibreoptic
phototherapy for neonatal jaundice. Volume (Issue 1).
21. Ludwig, M. (1990). Phototherapy in the home setting. Journal of Pediatric Health Care, 4(6),
304-308.
April 2002
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Jaundice in the Healthy Term Newborn
22. Hamelin, K. & Seshia, M. (1998). Home phototherapy for uncomplicated neonatal jaundice.
Canadian Nurse, Jan., 39-40.
23. Murphy, B. & Welch, R. (1992). Home phototherapy for the jaundiced full-term newborn.
Journal of Home Health Care Practitioner, 5(1), 26-33.
24. British Columbia Reproductive Care Program. (2001). British Columbia Newborn Care Path:
Outcomes, Teaching & Interventions. Vancouver, Author.
25. Campbell River Hospital. (2000). Protocol: Hyperbilirubinemia – Home Phototherapy
Management. Campbell River, BC: Author
26. Mississauga Hospital. (1994). Protocol: Home Phototherapy Programme. Mississauga, ON:
Author.
27. University of Manitoba, Health Science Centre. (????). Protocol: Home Phototherapy Program.
Winnepeg: Author. Access from: http://www.umanitoba.ca/womens_health/hschomet.htm
WEB RESOURCES
http://www.aap.org/policy/hyperb.htm
www.cps.ca/english/statements/FN/fn98-02.htm
http://www.cps.ca/english/statements/FN/fn96-02.htm
www.cs.nsw.gov.au/rpa/neonatal/html/newprot/jaund2.htm
http://www.umanitoba.ca/womens_health/hschomet.htm
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Jaundice in the Healthy Term Newborn
APPENDIX 1 (Example)
Management of Newborn Jaundice at Home Program
Referral for the Healthy Term Infant
PHN Identifies jaundice in
the newborn
1. Preterm Infant? Rh/ABO incompatibility?
2. Look or act ill (e.g. lethargic, apnea, tachycardia,
temperature unstable, poor feeding, changed behavior,
persistant vomiting, insufficient voiding/stooling)?
Yes
Refer to MD ASAP
No
Family hx of early or severe
jaundice? Ethnicity relevant
(Mediterranean, SE Asian)
Refer to MD for
investigation.eg.
G6PD, Spherocytosis
Yes
No
Infant less than
24 hrs
Yes
Refer to MD for
non - isoimmune
hemolytic
disease
investigation
Yes
Refer to MD for
follow-up with total
serum bilirubin
No
Routine
Clinical
Supervision
No
Is jaundice
clinically
significant?
No
Routine
care and
feeds
Routine
care and
feeds
No
No
Jaundice persisted
> 2 weeks?
Jaundice >3
weeks?
Yes
Any abnormal physical
findings? Dark urine,
light stools?
Refer to MD
Refer to MD
Yes
Developed by the Coordinated Maternity Standards Committee, South Fraser
Health Region and Dr. K. Danso, Pediatrician Surrey Memorial Hospital.
Revised 1997. Copied with permission.
April 2002
Yes
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Jaundice in the Healthy Term Newborn
APPENDIX 2
Approach to the Management of Hyperbilirubinemia
in Term Newborn Infants
A Joint Statement with the College of Family Physicians of Canada
Paediatrics & Child Health 1999;4(2):161-164
Reference No. FN98-02
Reaffirmed February 2001
Reprints of this position statement are available from the Canadian Paediatric Society,
100-2204 Walkley Road, Ottawa ON K1G 4G8; phone: (613) 526-9397; fax: (613) 5263332.
Contents
• Background
• Phototherapy
• Clinical management of hyperbilirubinemia in infants
• Exchange transfusion
• Conclusions
• References
Conflicting reports have led to confusion about the optimal management of jaundice in otherwise healthy term
infants (1-9). The ‘kinder gentler approach’ to neonatal hyperbilirubinemia proposed in 1992 by Newman and
Maisels (8) resulted in a 1994 statement by the American Academy of Pediatrics (2) that addressed the
management of healthy term infant without risk factors. Recently, there has been an increase in the number of
term infants reported with kernicterus (10). It is important to note that while some of the infants reported with
kernicterus had features that would place them in a high risk category, some presented with severe jaundice
only and no identifiable risk factors (10). The infants reported were commonly breastfed and frequently
discharged from hospital very soon after birth (10). Nonetheless, the current standards (2) for the management
of hyperbilirubinemia in the healthy term infant have become controversial.
This document updates information previously published by the Canadian Paediatric Society (1). It provides an
overview of the proposed management of hyperbilirubinemia based on available evidence, even though
randomized controlled trials are not available to allow a conclusive assessment of the risk associated with
hyperbilirubinemia in the clinical situations encountered in practice. The objective of this overview is to
establish a management plan that will minimize the risk of kernicterus in term infants both with and without
risk factors. Although scientific evidence has not established a clear link between specific bilirubin
concentrations and the development of kernicterus in healthy term babies, information to date has been
incorporated into the following guidelines.
Background
Kernicterus is a neurological condition characterized by deep yellow staining of the basal nuclei. The
accompanying clinical syndrome results from the destructive changes of these neuronal populations. Initially,
the signs are lethargy, hypotonia and seizures; later, the infants may develop athetoid cerebral palsy, mental
retardation and deafness. When neurological signs evident in the infant, permanent damage has already
occurred, leading to death or long term disability. Therefore, management strategies are aimed at preventing
kernicterus.
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Until recently, these strategies suggested maintaining serum unconjugated bilirubin concentrations below 340
µmol/L (20 mg/dL) in healthy term infants through the use of phototherapy or exchange transfusion (11). While
exchange transfusions had been a frequent occurrence from the 1950s to the 1970s and may sometimes still be
required, phototherapy has become the mainstay of medical management of hyperbilirubinemia since that time.
The cases of kernicterus originally described occurred mainly in infants with hemolytic disease. Higher serum
unconjugated bilirubin concentrations may be safe in healthy term infants without hemolytic disease. It is not
possible to predict at what level an individual infant may develop kernicterus.
Several authors have expressed serious concerns over the approach of allowing higher serum unconjugated
bilirubin concentrations to occur before investigating and treating these term infants (11-16). Brown and
Johnson (10) have reported 23 cases of kernicterus occurring since 1989, 16 in term and seven in near term
infants. In these infants, peak unconjugated bilirubin concentrations of 375 to 860 µmol/L (22 to 50 mg/dL)
were seen. All but one infant was breastfed. Other associations found in these infants with kernicterus were
dehydration (seven infants), glucose-6-phosphate dehydrogenase (G6PD) deficiency (five infants), ABO
alloimmunization (one infant), hemolysis of unknown cause (five infants), familial etiology (one infant) and
otherwise unexplained early jaundice clinically evident before 24 h of age (six infants). Similar cases have been
reported by others (17,18). Although many of these babies were subsequently found to have additional risk
factors, these factors were not often identified at the time the baby was noted to be jaundiced.
Since the introduction in the 1990s of the kinder, gentler approach to the management of hyperbilirubinemia, a
great deal of confusion has arisen about approaches to the management of hyperbilirubinemia in healthy term
infants. This confusion has extended to the care of borderline preterm infants who have often been treated as
term infants. A recently published international survey reported considerable variability in the approach to
hyperbilirubinemia and the use of phototherapy among neonatal units worldwide (3).
Phototherapy
The goal of hyperbilirubinemia treatment is to avoid bilirubin concentrations that may result in kernicterus.
Phototherapy remains an effective therapeutic intervention that decreases bilirubin concentrations, thereby
preventing elevated bilirubin levels associated with permanent sequelae.
The effectiveness of phototherapy is related to the area of skin exposed, and the radiant energy and the
wavelength of the light (19-23). Phototherapy acts on unconjugated bilirubin to a depth of 2 mm from the
epidermis. Phototherapy changes the bilirubin through structural photoisomerization into water-soluble
lumirubin that is excreted in the urine (19). The fall in bilirubin level is proportionately greater in the skin than
in the serum (20). Therefore, the infant receiving phototherapy should have as much skin as possible exposed to
the lights. More intense phototherapy may be achieved by using multiple sources of phototherapy; double or
triple phototherapy is recommended to optimize the skin surface exposed and, therefore, the efficacy of
phototherapy. More detailed discussion of the physics of phototherapy has been published (1,24).
It is important to recognize the relationship between dehydration and hyperbilirubinemia. Dehydration may be
associated with increased serum bilirubin concentrations and may be exacerbated by phototherapy. All
jaundiced infants should be adequately hydrated before and during phototherapy. Breastfeeding is not
contraindicated in the presence of hyperbilirubinemia and should be continued. More frequent breastfeedings
may be beneficial (25).
The concentrations of bilirubin at which phototherapy might be initiated in healthy term infants and those with
risk factors are shown in Figure 1. Guidelines for phototherapy in low birth weight infants remain as previously
published (1). The bilirubin concentrations at which phototherapy is suggested by the Canadian Paediatric
Society in the present statement are more conservative than the current recommendations of the American
Academy of Pediatrics (2). If the infant is a healthy term newborn, phototherapy should be started as indicated
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in the upper curve of Figure 1. If the infant has one or more risk factors, a clinical decision should be made to
initiate phototherapy at the concentration indicated by the lower curve.
Figure 1: Guidelines for initiation of phototherapy for hyperbilirubinemia in term infants with and without risk
factors. Some risk factors include gestional age younger than 37 weeks, birth weight less than 2500 g,
hemolysis, jaundice at younger than 24 h of age, sepsis and the need for resuscitation at birth
The timely recognition of risk factors is essential to minimize the danger of kernicterus. The risk factors are as
follows:
• gestational age younger than 37 weeks and birth weight less than 2500 g;
• hemolysis due to maternal isoimmunization, G6PD deficiency, spherocytosis or other causes;
• jaundice at less than 24 h of age;
• sepsis; and
• the need for resuscitation at birth.
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Clinical management of hyperbilirubinemia in infants
A bilirubin level that justifies consideration of phototherapy should mandate the investigation of the cause of
hyperbilirubinemia. Investigation should include a clinically pertinent history of the mother, family history,
description of labour and delivery, and infant’s clinical course (26). A physical examination should be
supplemented by laboratory investigations (Table 1) including determination of unconjugated and conjugated
serum bilirubin concentrations, and blood group with direct antibody test (Coombs’ test) and hemoglobin and
hematocrit levels. A complete blood count, including differential white cell count and a blood smear for red cell
morphology, may be indicated. Further tests (eg, reticulocyte count, G6PD screen) may be indicated based on
initial results, ethnicity or clinical presentation. Testing for serum electrolytes and albumin or protein are
indicated in some situations such as suspected dehydration or when bilirubin levels approach exchange values.
In the absence of drugs or clinical states that alter the binding of bilirubin by albumin, the bilirubin to albumin
or the bilirubin to protein ratio reflects the free bilirubin concentration and the binding capacity of the serum
(27-29). At a bilirubin concentration close to exchange transfusion levels, some clinicians may wish to ensure
that serum bilirubin binding is normal (albumin 25 g/L or greater, protein 54 g/L or greater). Values below
these levels may be associated with low bilirubin binding and may be used by the clinician when deciding
whether further intervention (eg, exchange transfusion) should take place (27).
TABLE 1: Laboratory investigation for hyperbilirubinemia in term newborn infants
Indicated (if bilirubin concentrations reach phototherapy levels)
Serum total or unconjugated bilirubin concentration
Serum conjugated bilirubin concentration
Blood group with direct antibody test (Coombs’ test)
Hemoglobin and hematocrit determinations
Optional (in specific clinical circumstances)
Complete blood count including manual differential white cell count
Blood smear for red cell morphology
Reticulocyte count
Glucose-6-phosphate dehydrogenase screen
Serum electrolytes and albumin or protein concentrations
For infants with prolonged jaundice (lasting longer than seven days) or with conjugated hyperbilirubinemia
(greater than 30 µmol/L), additional investigation and management may be required, and a consultation with a
specialist may be needed (30).
During the past decade, most nurseries have shortened the time of hospital stay for term healthy newborn
infants. Early discharge of neonates means that jaundice is not often recognized at discharge (31). The Canadian
Paediatric Society reiterates the importance of allowing early discharge only if a healthy status is confirmed for
each baby and appropriate follow-up is provided (32). Appropriate parental education about feeding, signs of
dehydration and jaundice must be implemented in hospital nurseries. Testing for serum bilirubin concentrations
must be readily available for newborns on an out-patient basis. Readmission to hospital (usually the hospital of
birth) may be necessary for the investigation and management of hyperbilirubinemia.
Exchange transfusion
If phototherapy fails to control the rising bilirubin levels, exchange transfusion is indicated to lower serum
bilirubin concentrations. For healthy term infants without risk factors, exchange transfusion should be
considered at serum unconjugated bilirubin concentrations of 400 to 430 µmol/L. For term infants with risk
factors, the level should be 340 µmol/L. For infants who initially present with serum bilirubin concentrations in
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Jaundice in the Healthy Term Newborn
excess of exchange levels, intensive phototherapy should produce a decline of serum unconjugated bilirubin
from 20 to 35 µmol/L within 4 to 6 h, and levels should continue to fall thereafter and remain below the
threshold for exchange transfusion. If the bilirubin concentration does not decrease after adequate rehydration
and 4 to 6 h of intensive phototherapy, exchange transfusion should be considered. Preparation for this,
including ensuring availability of blood, should occur shortly after the admission of babies whose bilirubin
concentrations exceed exchange levels. Appropriate consultation should be obtained if the etiology of
hyperbilirubinemia is unclear, the infant is ill, and particularly if bilirubin concentrations are approaching
exchange levels. Because the risks of exchange transfusion are significant, the best management may be
reviewed with an expert opinion from a neonatologist.
Conclusions
Hyperbilirubinemia in apparently healthy term newborn infants continues to hold the potential threat of
complications from bilirubin encephalopathy and kernicterus. Careful assessment of risk factors, judicious use
of phototherapy, appropriate laboratory monitoring and specific treatment of other disorders (eg, sepsis) are
essential for the optimal management of hyperbilirubinemia. Appropriate laboratory facilities must be available
to measure bilirubin concentrations for out-patients in required clinical situations. Readmission to hospital may
be required if phototherapy is necessary. Guidelines for phototherapy are presented for term babies with and
without identifiable risk factors.
References
1. Fetus and Newborn Committee, Canadian Paediatric Society. Use of phototherapy for neonatal
hyperbilirubinemia. Can Med Assoc J 1986;134:1237-45.
2. American Academy of Pediatrics. Practice parameter: Management of hyperbilirubinemia in the healthy term
newborn. Pediatrics 1994;94:558-65.
3. Hansen TWR. Therapeutical approaches to neonatal jaundice: an international survey. Clin Pediatr
1996;35:309-16.
4. Valaes T, Koliopoulos C, Koltsidopoulos A. The impact of phototherapy in the management of neonatal
hyperbilirubinemia: comparison of historical cohorts. Acta Paediatrica 1996;85:273-6.
5. Gustafson PA, Boyle DW. Bilirubin index: a new standard for intervention. Med Hypotheses 1995;45:40916.
6. Torres-Torres M, Tayaba R, Weintraub A, Holzman IR. New perspectives on neonatal hyperbilirubinemia.
Mount Sinai J Med 1994;61:424-8.
7. Lazar L, Litwin A, Merlob P. Phototherapy for neonatal nonhemolytic hyperbilirubinemia: analysis of
rebound and indications for discontinuing therapy. Clin Pediatr 1993;32:264-7.
8. Newman TB, Maisels MJ. Evaluation and treatment of jaundice in the term newborn. Pediatrics 1992;89:80918.
9. McMillan DD, Lockyer JM, Magnan L, Akierman A, Parboosingh JT. Effect of educational program and
interview on adoption of guidelines for the management of neonatal hyperbilirubinemia. Can Med Assoc J
1991;144:707-12.
10. Brown AK, Johnson L. Loss of concern about jaundice and the reemergence of kernicterus in full-term
infants in the era of managed care. In: Fanaroff AA, Klaus MH, eds. The Year Book of Neonatal and Perinatal
Medicine. Philadelphia: Mosby Yearbook, 1996:17-28.
11. Valaes T. Bilirubin toxicity: The problem was solved a generation ago. Pediatrics 1992;89:819-21.
12. Wennberg RP. Bilirubin recommendations present problems: New guidelines simplistic and untested.
Pediatrics 1992;89:821-2.
13. Merenstein GB. ‘New’ bilirubin recommendations questioned. Pediatrics 1992;89:822-3.
14. Poland RL. In search of a ‘gold standard’ for bilirubin toxicity. Pediatrics 1992;89:823-4.
15. Brown AK, Seidman DS, Stevenson DK. Jaundice in healthy, term neonates: Do we need new action levels
or new approaches? Pediatrics 1992;89:827-9.
16. Johnson L. Yet another expert opinion on bilirubin toxicity. Pediatrics 1992;89:829-31.
April 2002
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Jaundice in the Healthy Term Newborn
17. MacDonald MG. Hidden risks: Early discharge and bilirubin toxicity due to glucose-6-phosphate
dehydrogenase deficiency. Pediatrics 1995;96:734-8.
18. Maisels MJ, Newman TB. Kernicterus in otherwise healthy breast-fed newborns. Pediatrics 1995;96:730-3.
19. Vogl TP. Phototherapy of neonatal hyperbilirubinemia: bilirubin in unexposed areas of the skin. J Pediatr
1974;85:707-10.
20. Rubaltelli FF, Carli M. The effect of light on cutaneous bilirubin. Biol Neonate 1971;18:457-62.
21. Sisson TR, Kendall N, Shaw E, et al. Phototherapy of jaundice in the newborn infant: 2. Effect of various
light intensities. J Pediatr 1973;81:35-8.
22. Bonta BW, Warshaw JB. Importance of radiant flux in the treatment of hyperbilirubinemia: failure of
overhead phototherapy units in intensive care units. Pediatrics 1976;57:502-5.
23. Warshaw JB, Gagliardi J, Patel A. A comparison of fluorescent and non-fluorescent light source for
phototherapy. Pediatrics 1980;65:795-8.
24. Ennever JF. Blue light, green light, white light, more light: treatment of neonatal jaundice. Clin Perinatol
1990;17:467-81.
25. Auerbach KG, Gartner LM. Breastfeeding and human milk: their association with jaundice in the neonate.
Clin Perinatol 1987;14:89-108.
26. Maisels MJ. Jaundice in the newborn. Pediatr Rev 1982;3:305-20.
27. Ahlfors CE. Criteria for exchange transfusion in jaundiced newborns. Pediatrics 1994;93:488-94.
28. Odell GB, Storey GNB, Rosenberg LA. Studies in kernicterus. III. The saturation of serum protein with
bilirubin during neonatal life and its relationship to brain damage at 5 years. J Pediatr 1970;76:12-21.
29. Wirth FH, Goldberg KE, Lubchenco LO. The neurologic outcome of infants evaluated for unbound
bilirubin. Pediatr Res 1975;9:385-91.
30. Haber BA, Lake AM. Cholestatic jaundice in the newborn. Clin Perinatol 1990;17:483-506.
31. Maisels MJ, Newman TB. Jaundice in full-term and near-term babies who leave the hospital within 36
hours: The pediatrician’s nemesis. Clin Perinatol 1998;25:295-302.
32. Fetus and Newborn Committee, Canadian Paediatric Society, and Society of Obstetricians and
Gynaecologists of Canada. Facilitating discharge home following a normal term birth. Paediatr Child Health
1996;1:165-8.
Fetus and Newborn Committee
Members: Drs John Watts, Department of Paediatrics, Children’s Hospital – Hamilton Health Sciences Centre,
Hamilton, Ontario (director responsible); Douglas McMillan, Department of Pediatrics, Foothills Hospital,
Calgary, Alberta (chair); Arne Ohlsson, Department of Paediatrics, Mount Sinai Hospital, Toronto, Ontario
(co-chair); Deborah Davis, Children’s Hospital of Eastern Ontario, Ottawa, Ontario; Daniel Faucher, Royal
Victoria Hospital, Montreal, Quebec (principal author); John Van Aerde, Stollery Children’s Health Centre,
Edmonton, Alberta; Michael Vincer, IWK-Grace Health Centre, Halifax, Nova Scotia
Consultant: Dr Michael C Klein, University of British Columbia, Vancouver, British Columbia (College of
Family Physicians of Canada)
Liaisons: Drs James Lemon, Riley Children’s Hospital, Indiana University Medical Center, Indianapolis,
Indiana (American Academy of Pediatrics); Saroj Saigal, Department of Paediatrics, McMaster University
Medical Centre, Children’s Hospital – Hamilton Health Sciences Centre, Hamilton, Ontario (CPS NeonatalPerinatal Medicine Section); Cheryl Levitt, Department of Family Medicine, Children’s Hospital – Hamilton
Health Sciences Centre, Hamilton, Ontario (College of Family Physicians of Canada); Catherine McCourt,
Director, Bureau of Reproductive & Child Health, Laboratory Centre for Disease Control, Ottawa, Ontario
(Health Canada); Mrs Debbie Fraser-Askin, Winnipeg, Manitoba (Neonatal Nurses); Dr Line Leduc,
Department of Obstetrics-Gynecology, Hôpital Sainte-Justine, Montreal, Quebec (Society of Obstetricians and
Gynaecologists of Canada)
Disclaimer: The recommendations in this position statement do not indicate an exclusive course of
treatment or procedure to be followed. Variations, taking into account individual circumstances, may be
appropriate.
April 2002
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Jaundice in the Healthy Term Newborn
APPENDIX 3
Hyperbilirubinemia Risk Designation for Term and Near-Term Well Newborns
April 2002
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Jaundice in the Healthy Term Newborn
APPENDIX 4
American Academy of Pediatrics. 1994. Practice parameter: Management of
Hyperbilirubinemia in the Healthy Term Newborn. Pediatrics, 94(4), 558-565.
(Chart and Algorithm)
April 2002
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Jaundice in the Healthy Term Newborn
Algorithm
1
Pediatric clinician evaluates
term newborn with jaundice
2
3
Does the infant have signs of underlying
serious illness (lethargy, apnea, tachypnea,
temperature instability, behavior changes,
hepatosplenomegaly, persistant vomiting,
or persistent feeding difficulty)?
Exit this algorithm to individualized
clinical evaluation, including
assessment of jaundice and underlying
disease
Yes
5
No
4
Is the infant < 37 weeks' gestational age?
Exit this algorithm to individualized
clinical evaluation, including
assessment of jaundice in light of
prematurity
Yes
No
6
8
7
Is the mother's
ABO and Rh
blood typing and
isoimmune
antibody screen
status known?
Is the mother's
blood Rh
positive?
Yes
No
(Go to Box 10)
9
Does the
mother's blood
have any
immune
antibodies?
Yes
No
Yes
(Go to Box 10)
(Go to Box 10)
No
Consider holding the infant's
cord blood in the blood bank in
case future testing is necessary
(Go to Box 13)
10
Perform blood typing (ABO and Rh) and direct Coombs' testing
on the infant's cord (preferably) or venous blood
12
11
Is the infant's
blood direct
Coombs' test
positive?
13
Yes
No
Are any of the following risk factors present to
suggest that nonisoimmune hemolytic disease
is possible in this infant?
(1) Family history of hemolytic anemia;
OR
(2) Family history of early or severe
jaundice;
OR
(3) Ethnicity or geographic origin
associated with hemolytic anemia;
OR
(4) Early or severe jaundice
No
(Go to Box 16)
April 2002
Exit this algorithm to individualized clinical evaluation,
including assessment of jaundice and isoimmune
hemolytic disease
14
Perform appropriate laboratory
assessment of infant including
(but not limited to consideration of):
(1) Complete blood count, differential,
smear, reticulocyte count;
(2) G6PD screen;
(3) Hemoglobin electrophoresis
No
15
Does the evaluation suggest
hemolytic disease?
Yes
No
(Go to Box 16)
Page 19 of 20
(Go to Box 17)
Jaundice in the Healthy Term Newborn
Algorithm
16
17
Is the infant
jaundiced and
< 24 hours of
age?
Exit this algorithm to individualized
clinical evaluation, including
assessment of jaundice and
nonisoimmune hemolytic disease
Yes
No
18
19
Is jaundice"clinically
significant" by medical
judgment?
Yes
(1) Measure infant's
total serum bilirubin
(2) Go to Box 27
No
20
Healthy term infant with jaundice not clinically
significant by medical judgment
21
Follow infant in routine clinical supervision
22
(Go to Box 22)
Is jaundice
persisting
> 2 weeks?
23
Does this infant have
abnormal physical
exam results, dark
urine or light stools?
Yes
25
Yes
Perform appropriate physical and
laboratory assessment of the
infant, including possibility of
cholestatic jaundice
No
24
No
Is jaundice persisting
> 3 weeks?
Yes
26
Provide routine care,
recommend routine
feeding and follow-up
(From Box 19)
Algorithm. Management of hyperbilirubinemia in
the healthy term infant.
April 2002
No
27
Table 2. Management of Hyperbilirubinemia in the Healthy Term Newborn*
Age,
hours
TSB Level, mg/dL (umol/L)
<24****
25-48
49-72
> 72
Consider
Phototherapy**
Phototherapy
..........
> 12 (170)
> 15 (260)
> 17 (290)
..........
>15 (260)
> 18 (310)
> 20 (340)
Exchange
Transfusion
if Intensive
Phototherapy
Fails***
..........
> 20 (340)
> 25 (430)
> 25 (430)
Exchange
Transfusion
and Intensive
Phototherapy
..........
> 25 (430)
> 30 (510)
> 30 (510)
*TSB indicates total serum bilirubin.
**Phototherapy at these TSB levels is a clinical option, meaning that the intervention is available
and may be used on the basis of individual clinical judgement.For a more detailed description
of phototherapy, see the Appendix..
***Intensive phototherapy (Appendix) should produce a decline of TSB of 1 to 2 mg/dL within 4 to 6
hours and the TSB level should continue to fall and remain below the threshold level for exchange
transfusion. If this does not occur, it is considered a failure of phototherapy.
****Term infants who are clinically jaundiced at< 24 hours old are not considered healthy and
require further evaluation (see text).
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