Jaundice in the Healthy Term Newborn

British Columbia Reproductive Care Program

April 1993 – OriginalFebruary 1994 - RevisedApril 2002 - Revised of 20

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, withapproximately 50% of term infants having visible jaundice. Despite progress in neonatal care and thevirtual absence of classic bilirubin encephalopathy, safe bilirubin levels have not been established withabsolute certainty. There has been an increase in the number of term infants reported withkernicterus1,2 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 follow-up4,5.

When carefully reviewed, the data from numerous studies of bilirubin toxicity are so complex that it isdifficult to derive a single rational approach to jaundiced neonates6. One principle is well accepted: ifthere is any evidence that a neonate’s jaundice is not physiologic, the cause should be investigatedprior 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 ofmetabolism

• 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

Jaundice in the Healthy Term Newborn

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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 thecause for this has not been determined with certainty6.


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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 andgive 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 to48 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 (Seeexample 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 inhealthy term infants8,10. Accuracy may be limited by the changing pigmentation of the skin, theduration of jaundice and the effect of phototherapy11.


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II. BILIRUBIN MEASUREMENT

Several studies have looked at the predictive ability of predischarge serum bilirubin testing12,13,14. Todate, routine bilirubin investigation for healthy term newborns is not indicated. However, if theinfant’s level of jaundice is a concern at discharge, it may be prudent and helpful to obtain a bilirubinlevel 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 tothe observation that jaundice starts on the head, and extends towards the feet as the level rises. This isuseful in deciding whether or not a baby needs to have the serum bilirubin (SBR) measured. Kramerdivided the infant into 5 zones. The SBR range associated with progression to the zones is as follows:

Zone 1 2 3 4 5SBR

(umol/L)100 150 200 250 >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 le• 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

of 20

ast 8 times in 24 hours


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• Elimination (See guide below)

Guide for Healthy Term Newborn Output

Day Number of Stools/24 hours Number of Wet diapers/24 hours

1 at least one meconium at least 1 2 at least one meconium at least 2 3 at least 1 transitional at least 3 4 at least 2 + yellow/seedy at least 4 5 at least 2 + yellow/seedy 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 infantshould 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 neurologicalcomplications. Adequate hydration is an important consideration in the infant with moderate to highbilirubin levels.

Fundamental to management is a good history and physical examination, together with appropriateinvestigations 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 phototherapyand/or exchange transfusion. Several expert bodies have developed guidelines to assist care providers


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determine the appropriate time to implement each therapy as well as how to provide the therapy mosteffectively.1,12,17

The most common guidelines utilized in risk identification and management of hyperbilirubinemia arelisted 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 highand 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 longstanding practice19. Controlled studies on this treatment have not been done. Mild jaundice requiresno sunlight exposure, as it sends a false note to parents that their baby has a significant problem whenin 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 foundthat fibroptic phototherapy was more effective at lowering serum bilirubin than no treatment, but less


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effective than conventional phototherapy. A combination of fibroptic and conventional phototherapywas more effective than conventional phototherapy alone. No conclusion could be made on thesuperiority of one fibroptic device over another. No trials have been identified which support the viewthat 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 orthose 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 fibropticblankets and portable bilibeds, home phototherapy has been implemented in a few communitiesthroughout Canada.25-27 To date, there are no published evidence-based guidelines on the use of homephototherapy.

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 tothe 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 thehospital 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 andreadmission for mild and severe jaundice. Archive of Pediatric and Adolescent Medicine, 153, 1283-1288).

5. Liu, S., Wen, S., McMillan, D., Trouton, K., Fowler, D. & McCourt, C. (2000). Increasedneonatal 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 andGynecologists, Elk Grove Village, IL: American Academy of Pediatrics. Washington, DC.

7. Banks, J., Montgomer, D., Coody, D & Yetman, R. (1996). Hyperbilirubinemia in the termnewborn. Journal of Pediatric Health Care, 10(5), 228-230.

http://www.cps.ca/english/statements/FN/fn98-02.htm


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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 & ChildHealth,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). NoninvasiveMeasurement of Total Bilirubin in a Multiracial Predischarge Newborn Population to Assess the Riskof 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-specificserum 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 offirst-day bilirubin measurement in predicting the development of significant hyperbilirubinemia inhealth term newborns. Pediatrics, 106(2).

15. Kramer L. 1969. Advancement of dermal icterus in the jaundiced newborn. American Journal ofDiseases in Children, 118, 454-458.

16. Royal Prince Alfred Hospital. 1998. The department of neonatal medicine protocol book:jaundice. Sydney: Author. Accessed May 2001 fromwww.cs.nsw.gov.au/rpa/neonatal/html/newprot/jaund2.htm.

17. American Academy of Pediatrics. (1994). Practice parameter: Management ofhyperbilirubinemia 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 forBreastfeeding 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: Fibreopticphototherapy for neonatal jaundice. Volume (Issue 1).

21. Ludwig, M. (1990). Phototherapy in the home setting. Journal of Pediatric Health Care, 4(6),304-308.


http://www.cs.nsw.gov.au/rpa/neonatal/html/newprot/jaund2.htm

http://www.aap.org/policy/hyperb.htm


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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 PhototherapyManagement. 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


www.cps.ca/english/statements/FN/fn98-02.htm


www.cs.nsw.gov.au/rpa/neonatal/html/newprot/jaund2.htm

http://www.umanitoba.ca/womens_health/hschomet.htm





http://www.cs.nsw.gov.au/rpa/neonatal/html/newprot/jaund2.htm



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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)?

No

Family hx of early or severejaundice? Ethnicity relevant(Mediterranean, SE Asian)

No

Infant less than24 hrs

No

Is jaundiceclinically

significant?

No

Jaundice persisted> 2 weeks?

Jaundice >3weeks?

Routinecare and

feedsNo

Routinecare and

feedsNo

RoutineClinical

Supervis-ion

No

Refer to MD ASAPYes

Refer to MD forinvestigation.eg.

G6PD, SpherocytosisYes

Refer to MD fornon - isoimmune

hemolyticdisease

investigation

Yes

Refer to MD forfollow-up with total

serum bilirubinYes

Any abnormal physicalfindings? Dark urine,

light stools?Refer to MDYes Yes

Refer to MDYes

APPENDIX 1 (Example)

Developed by the Coordinated Maternity Standards Committee, South FraserHealth Region and Dr. K. Danso, Pediatrician Surrey Memorial Hospital.

Revised 1997. Copied with permission.


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APPENDIX 2

Approach to the Management of Hyperbilirubinemiain Term Newborn Infants

A Joint Statement with the College of Family Physicians of CanadaPaediatrics & Child Health 1999;4(2):161-164Reference No. FN98-02Reaffirmed 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) 526-3332.

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 terminfants (1-9). The ‘kinder gentler approach’ to neonatal hyperbilirubinemia proposed in 1992 by Newman andMaisels (8) resulted in a 1994 statement by the American Academy of Pediatrics (2) that addressed themanagement of healthy term infant without risk factors. Recently, there has been an increase in the number ofterm infants reported with kernicterus (10). It is important to note that while some of the infants reported withkernicterus had features that would place them in a high risk category, some presented with severe jaundiceonly and no identifiable risk factors (10). The infants reported were commonly breastfed and frequentlydischarged from hospital very soon after birth (10). Nonetheless, the current standards (2) for the managementof hyperbilirubinemia in the healthy term infant have become controversial. This document updates information previously published by the Canadian Paediatric Society (1). It provides anoverview of the proposed management of hyperbilirubinemia based on available evidence, even thoughrandomized controlled trials are not available to allow a conclusive assessment of the risk associated withhyperbilirubinemia in the clinical situations encountered in practice. The objective of this overview is toestablish a management plan that will minimize the risk of kernicterus in term infants both with and withoutrisk factors. Although scientific evidence has not established a clear link between specific bilirubinconcentrations and the development of kernicterus in healthy term babies, information to date has beenincorporated into the following guidelines. Background

Kernicterus is a neurological condition characterized by deep yellow staining of the basal nuclei. Theaccompanying 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, mentalretardation and deafness. When neurological signs evident in the infant, permanent damage has alreadyoccurred, leading to death or long term disability. Therefore, management strategies are aimed at preventingkernicterus.


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Until recently, these strategies suggested maintaining serum unconjugated bilirubin concentrations below 340µmol/L (20 mg/dL) in healthy term infants through the use of phototherapy or exchange transfusion (11). Whileexchange transfusions had been a frequent occurrence from the 1950s to the 1970s and may sometimes still berequired, 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 serumunconjugated bilirubin concentrations may be safe in healthy term infants without hemolytic disease. It is notpossible to predict at what level an individual infant may develop kernicterus.

Several authors have expressed serious concerns over the approach of allowing higher serum unconjugatedbilirubin concentrations to occur before investigating and treating these term infants (11-16). Brown andJohnson (10) have reported 23 cases of kernicterus occurring since 1989, 16 in term and seven in near terminfants. 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 weredehydration (seven infants), glucose-6-phosphate dehydrogenase (G6PD) deficiency (five infants), ABOalloimmunization (one infant), hemolysis of unknown cause (five infants), familial etiology (one infant) andotherwise unexplained early jaundice clinically evident before 24 h of age (six infants). Similar cases have beenreported by others (17,18). Although many of these babies were subsequently found to have additional riskfactors, 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, agreat deal of confusion has arisen about approaches to the management of hyperbilirubinemia in healthy terminfants. This confusion has extended to the care of borderline preterm infants who have often been treated asterm infants. A recently published international survey reported considerable variability in the approach tohyperbilirubinemia and the use of phototherapy among neonatal units worldwide (3).

PhototherapyThe goal of hyperbilirubinemia treatment is to avoid bilirubin concentrations that may result in kernicterus.Phototherapy remains an effective therapeutic intervention that decreases bilirubin concentrations, therebypreventing elevated bilirubin levels associated with permanent sequelae.

The effectiveness of phototherapy is related to the area of skin exposed, and the radiant energy and thewavelength of the light (19-23). Phototherapy acts on unconjugated bilirubin to a depth of 2 mm from theepidermis. Phototherapy changes the bilirubin through structural photoisomerization into water-solublelumirubin that is excreted in the urine (19). The fall in bilirubin level is proportionately greater in the skin thanin the serum (20). Therefore, the infant receiving phototherapy should have as much skin as possible exposed tothe lights. More intense phototherapy may be achieved by using multiple sources of phototherapy; double ortriple phototherapy is recommended to optimize the skin surface exposed and, therefore, the efficacy ofphototherapy. 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 beassociated with increased serum bilirubin concentrations and may be exacerbated by phototherapy. Alljaundiced infants should be adequately hydrated before and during phototherapy. Breastfeeding is notcontraindicated in the presence of hyperbilirubinemia and should be continued. More frequent breastfeedingsmay be beneficial (25).

The concentrations of bilirubin at which phototherapy might be initiated in healthy term infants and those withrisk factors are shown in Figure 1. Guidelines for phototherapy in low birth weight infants remain as previouslypublished (1). The bilirubin concentrations at which phototherapy is suggested by the Canadian PaediatricSociety in the present statement are more conservative than the current recommendations of the AmericanAcademy 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 toinitiate phototherapy at the concentration indicated by the lower curve.

Figure 1: Guidelines for initiation of phototherapy for hyperbilirubinemia in term infants with and without riskfactors. 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 asfollows:

• 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 ofhyperbilirubinemia. 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 besupplemented by laboratory investigations (Table 1) including determination of unconjugated and conjugatedserum bilirubin concentrations, and blood group with direct antibody test (Coombs’ test) and hemoglobin andhematocrit levels. A complete blood count, including differential white cell count and a blood smear for red cellmorphology, may be indicated. Further tests (eg, reticulocyte count, G6PD screen) may be indicated based oninitial results, ethnicity or clinical presentation. Testing for serum electrolytes and albumin or protein areindicated 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 albuminor 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 ensurethat serum bilirubin binding is normal (albumin 25 g/L or greater, protein 54 g/L or greater). Values belowthese levels may be associated with low bilirubin binding and may be used by the clinician when decidingwhether 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 aspecialist may be needed (30).

During the past decade, most nurseries have shortened the time of hospital stay for term healthy newborninfants. Early discharge of neonates means that jaundice is not often recognized at discharge (31). The CanadianPaediatric Society reiterates the importance of allowing early discharge only if a healthy status is confirmed foreach baby and appropriate follow-up is provided (32). Appropriate parental education about feeding, signs ofdehydration and jaundice must be implemented in hospital nurseries. Testing for serum bilirubin concentrationsmust be readily available for newborns on an out-patient basis. Readmission to hospital (usually the hospital ofbirth) 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 serumbilirubin concentrations. For healthy term infants without risk factors, exchange transfusion should beconsidered at serum unconjugated bilirubin concentrations of 400 to 430 µmol/L. For term infants with riskfactors, the level should be 340 µmol/L. For infants who initially present with serum bilirubin concentrations in


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excess of exchange levels, intensive phototherapy should produce a decline of serum unconjugated bilirubinfrom 20 to 35 µmol/L within 4 to 6 h, and levels should continue to fall thereafter and remain below thethreshold for exchange transfusion. If the bilirubin concentration does not decrease after adequate rehydrationand 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 bilirubinconcentrations exceed exchange levels. Appropriate consultation should be obtained if the etiology ofhyperbilirubinemia is unclear, the infant is ill, and particularly if bilirubin concentrations are approachingexchange levels. Because the risks of exchange transfusion are significant, the best management may bereviewed with an expert opinion from a neonatologist.

Conclusions Hyperbilirubinemia in apparently healthy term newborn infants continues to hold the potential threat ofcomplications from bilirubin encephalopathy and kernicterus. Careful assessment of risk factors, judicious useof phototherapy, appropriate laboratory monitoring and specific treatment of other disorders (eg, sepsis) areessential for the optimal management of hyperbilirubinemia. Appropriate laboratory facilities must be availableto measure bilirubin concentrations for out-patients in required clinical situations. Readmission to hospital maybe required if phototherapy is necessary. Guidelines for phototherapy are presented for term babies with andwithout identifiable risk factors.

References

1. Fetus and Newborn Committee, Canadian Paediatric Society. Use of phototherapy for neonatalhyperbilirubinemia. Can Med Assoc J 1986;134:1237-45. 2. American Academy of Pediatrics. Practice parameter: Management of hyperbilirubinemia in the healthy termnewborn. Pediatrics 1994;94:558-65. 3. Hansen TWR. Therapeutical approaches to neonatal jaundice: an international survey. Clin Pediatr1996;35:309-16. 4. Valaes T, Koliopoulos C, Koltsidopoulos A. The impact of phototherapy in the management of neonatalhyperbilirubinemia: 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;45:409-16. 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 ofrebound 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;89:809-18. 9. McMillan DD, Lockyer JM, Magnan L, Akierman A, Parboosingh JT. Effect of educational program andinterview on adoption of guidelines for the management of neonatal hyperbilirubinemia. Can Med Assoc J1991;144:707-12. 10. Brown AK, Johnson L. Loss of concern about jaundice and the reemergence of kernicterus in full-terminfants in the era of managed care. In: Fanaroff AA, Klaus MH, eds. The Year Book of Neonatal and PerinatalMedicine. 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 levelsor new approaches? Pediatrics 1992;89:827-9. 16. Johnson L. Yet another expert opinion on bilirubin toxicity. Pediatrics 1992;89:829-31.


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17. MacDonald MG. Hidden risks: Early discharge and bilirubin toxicity due to glucose-6-phosphatedehydrogenase 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 Pediatr1974;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 variouslight intensities. J Pediatr 1973;81:35-8. 22. Bonta BW, Warshaw JB. Importance of radiant flux in the treatment of hyperbilirubinemia: failure ofoverhead 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 forphototherapy. Pediatrics 1980;65:795-8. 24. Ennever JF. Blue light, green light, white light, more light: treatment of neonatal jaundice. Clin Perinatol1990;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 withbilirubin 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 unboundbilirubin. 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 36hours: The pediatrician’s nemesis. Clin Perinatol 1998;25:295-302. 32. Fetus and Newborn Committee, Canadian Paediatric Society, and Society of Obstetricians andGynaecologists of Canada. Facilitating discharge home following a normal term birth. Paediatr Child Health1996;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, RoyalVictoria Hospital, Montreal, Quebec (principal author); John Van Aerde, Stollery Children’s Health Centre,Edmonton, Alberta; Michael Vincer, IWK-Grace Health Centre, Halifax, Nova ScotiaConsultant: Dr Michael C Klein, University of British Columbia, Vancouver, British Columbia (College ofFamily 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 UniversityMedical Centre, Children’s Hospital – Hamilton Health Sciences Centre, Hamilton, Ontario (CPS Neonatal-Perinatal Medicine Section); Cheryl Levitt, Department of Family Medicine, Children’s Hospital – HamiltonHealth 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 andGynaecologists of Canada)

Disclaimer: The recommendations in this position statement do not indicate an exclusive course oftreatment or procedure to be followed. Variations, taking into account individual circumstances, may beappropriate.


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APPENDIX 3Hyperbilirubinemia Risk Designation for Term and Near-Term Well Newborns


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APPENDIX 4

American Academy of Pediatrics. 1994. Practice parameter: Management ofHyperbilirubinemia in the Healthy Term Newborn. Pediatrics, 94(4), 558-565.

(Chart and Algorithm)


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AlgorithmPediatric clinician evaluatesterm newborn with jaundice

Does the infant have signs of underlyingserious illness (lethargy, apnea, tachypnea,temperature instability, behavior changes,hepatosplenomegaly, persistant vomiting,

or persistent feeding difficulty)?

1

2

Exit this algorithm to individualizedclinical evaluation, including

assessment of jaundice and underlyingdisease

Yes

3

No

Is the infant < 37 weeks' gestational age?

4 Exit this algorithm to individualizedclinical evaluation, including

assessment of jaundice in light ofprematurity

5

Yes

Is the mother'sABO and Rh

blood typing andisoimmune

antibody screenstatus known?

Is the mother'sblood Rhpositive?

Does themother's blood

have anyimmune

antibodies?

Consider holding the infant'scord blood in the blood bank incase future testing is necessary

6 7 8 9No

Yes Yes No

(Go to Box 10) (Go to Box 10) (Go to Box 10) (Go to Box 13)

No No Yes

Perform blood typing (ABO and Rh) and direct Coombs' testingon the infant's cord (preferably) or venous blood

10

Is the infant'sblood direct

Coombs' testpositive?

Exit this algorithm to individualized clinical evaluation,including assessment of jaundice and isoimmune

hemolytic disease

11 12

Yes

Are any of the following risk factors present tosuggest 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 originassociated with hemolytic anemia;

OR(4) Early or severe jaundice

Perform appropriate laboratoryassessment of infant including

(but not limited to consideration of):(1) Complete blood count, differential,smear, reticulocyte count;(2) G6PD screen;(3) Hemoglobin electrophoresis

1314

No

No

No

(Go to Box 16)

Does the evaluation suggesthemolytic disease?

15

Yes

(Go to Box 17)(Go to Box 16)

No


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AlgorithmIs the infant

jaundiced and< 24 hours of

age?

Exit this algorithm to individualizedclinical evaluation, includingassessment of jaundice and

nonisoimmune hemolytic disease

Is jaundice"clinicallysignificant" by medical

judgment?

(1) Measure infant'stotal serum bilirubin(2) Go to Box 27

Healthy term infant with jaundice not clinicallysignificant by medical judgment

Follow infant in routine clinical supervision

1617

18 19

20

21

(Go to Box 22)

Yes

Yes

No

No

Is jaundicepersisting

> 2 weeks?

Does this infant haveabnormal physicalexam results, dark

urine or light stools?

Is jaundice persisting> 3 weeks?

Perform appropriate physical andlaboratory assessment of theinfant, including possibility of

cholestatic jaundice

Provide routine care,recommend routine

feeding and follow-up Table 2. Management of Hyperbilirubinemia in the Healthy Term Newborn*Age,hours TSB Level, mg/dL (umol/L)

Consider Phototherapy Exchange ExchangePhototherapy** Transfusion Transfusion

if Intensive and IntensivePhototherapy PhototherapyFails***

<24**** .......... .......... .......... ..........25-48 > 12 (170) >15 (260) > 20 (340) > 25 (430)49-72 > 15 (260) > 18 (310) > 25 (430) > 30 (510)> 72 > 17 (290) > 20 (340) > 25 (430) > 30 (510)

*TSB indicates total serum bilirubin.**Phototherapy at these TSB levels is a clinical option, meaning that the intervention is availableand may be used on the basis of individual clinical judgement. For a more detailed descriptionof phototherapy, see the Appendix..***Intensive phototherapy (Appendix) should produce a decline of TSB of 1 to 2 mg/dL within 4 to 6hours and the TSB level should continue to fall and remain below the threshold level for exchangetransfusion. 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 andrequire further evaluation (see text).

22 23

24

25

26

YesYes

No

YesNo

No 27

Algorithm. Management of hyperbilirubinemia inthe healthy term infant.

(From Box 19)

Jaundice in the Healthy Term Newborn

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