POSITION STATEMENT (FN-2007-02)

Guidelines for detection, management

and prevention of hyperbilirubinemia in
term and late preterm newborn infants
(35 or more weeks’ gestation) – Summary Français en page 411

ABSTRACT data (6) suggesting an incidence of approximately one per

Hyperbilirubinemia is very common and usually benign 10,000 live births; the incidence of chronic encephalopathy
in the term newborn infant and the late preterm infant at has been estimated to be between one per 50,000 live births
35 and 36 completed weeks’ gestation. Critical hyperbiliru- and one per 100,000 live births (6-9). Acute encephalopathy
binemia is uncommon but has the potential for causing long- does not occur in full-term infants whose peak TSB concen-
term neurological impairment. Early discharge of the healthy tration remains below 340 µmol/L and is very rare unless the
newborn infant, particularly those in whom breastfeeding peak TSB concentration exceeds 425 µmol/L, above this
may not be fully established, may be associated with delayed level the risk for toxicity progressively increases (10). Two-
diagnosis of significant hyperbilirubinemia. Guidelines for thirds of patients with chronic encephalopathy had a recorded
the prediction, prevention, identification, monitoring and peak TSB concentration that exceeded 600 µmol/L (11).
treatment of severe hyperbilirubinemia are presented. Prevention of acute bilirubin encephalopathy requires
appropriate clinical assessment, interpretation of TSB
For more information, please refer to the full text position state- concentration and treatment, which must involve the
ment at <www.cps.ca/english/publications/FetusAndNewborn/>. entirety of the systems involved in the provision of health
care and community support.
BACKGROUND AND EPIDEMIOLOGY Several factors that increase the risk of severe hyper-
Definitions of terms as used in this statement bilirubinemia have been identified, including: visible jaun-
• Kernicterus – the pathological finding of deep-yellow dice at younger than 24 h of age, visible jaundice before
staining of neurons and neuronal necrosis of the basal discharge at any age, gestation less than 38 weeks, sibling
ganglia and brainstem nuclei. with severe hyperbilirubinemia, visible bruising, cephalhe-
matoma, male sex, maternal age older than 25 years of age,
• Acute bilirubin encephalopathy – a clinical syndrome,
ethnic background (Asian or European), and exclusive and
in the presence of severe hyperbilirubinemia, of
partial breastfeeding. These risk factors are all very common
lethargy, hypotonia and poor suck, which may progress
and are, thus, of limited usefulness for directing surveil-
to hypertonia (with opisthotonos and retrocollis) with a
lance, investigation or therapy by themselves, but can be
high-pitched cry and fever, and eventually to seizures
useful in combination with timed TSB analysis.
and coma.
• Chronic bilirubin encephalopathy – the clinical METHODS OF STATEMENT DEVELOPMENT
sequelae of acute encephalopathy with athetoid cerebral Literature searches were last updated in January 2007. The
palsy with or without seizures, developmental delay, hierarchy of evidence from the Centre for Evidence-Based
hearing deficit, oculomotor disturbances, dental Medicine (Table 1) (12) was applied. The reference lists of
dysplasia and mental deficiency (1). recent publications were also examined (9).
• Severe hyperbilirubinemia – a total serum bilirubin
(TSB) concentration greater than 340 µmol/L at any CAN SEVERE HYPERBILIRUBINEMIA BE
time during the first 28 days of life. ACCURATELY PREDICTED?
Timed TSB measurements
• Critical hyperbilirubinemia – a TSB concentration Carefully timed TSB measurements can be used to predict
greater than 425 µmol/L during the first 28 days. the chances of developing severe hyperbilirubinemia. A
The prevention, detection and management of jaundice study (13) in direct antiglobulin test (DAT)-negative
in term and late preterm newborn infants remains a chal- term and late preterm infants demonstrated that a timed
lenge (2-4). Sixty per cent of term newborns develop jaun- measurement of TSB concentration at discharge (between
dice, and 2% exceed a TSB concentration of 340 µmol/L (5). 18 h and three days of age) could predict a later TSB con-
The incidence of acute encephalopathy is much lower, recent centration greater than 300 µmol/L (evidence level 1b,

Correspondence: Canadian Paediatric Society, 2305 St Laurent Boulevard, Ottawa, Ontario K1G 4J8. Telephone 613-526-9397,
fax 613-526-3332, Web sites www.cps.ca, www.caringforkids.cps.ca

Paediatr Child Health Vol 12 No 5 May/June 2007 401

CPS Statement: FN 2007-02

TABLE 1
Levels of evidence used in this statement summary
Level Therapy Prognosis Diagnosis
1a SR (with homogeneity) of SR (with homogeneity) of inception cohort studies SR (with homogeneity) of
randomized controlled trials (RCTs) level 1 diagnostic studies
1b Individual RCT (with narrow CI) Individual inception cohort study with >80% follow-up Validating cohort study with
good reference standards
2a SR (with homogeneity) of cohort studies SR (with homogeneity) of either retrospective SR (with homogeneity) of
cohort studies or untreated control groups in RCTs level >2 diagnostic studies
2b Individual cohort study (or low-quality Retrospective cohort study or follow-up of untreated Exploratory cohort study with
RCT; eg, <80% follow-up) control patients in an RCT good reference standards;
3a SR (with homogeneity) of case-control SR (with homogeneity)
studies of 3b and better studies
3b Individual case-control study Nonconsecutive study; or
without consistently applied
reference standards
4 Case series (and poor quality cohort Case series (and poor-quality prognostic cohort studies) Case-control study, poor or non-
and case-control studies) independent reference standard
5 Expert opinion without explicit critical appraisal, or based on physiology, bench research or ‘first principles’
SR Systematic review

350
testing, closer follow-up and earlier therapy; consultation
40th percentile
70th percentile
with a paediatric hematologist or neonatologist is suggested.
300 95th percentile
one
hz zon
e Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Hig
250
di ate
te rme zon
e Newborns with G6PD deficiency have an increased incidence
Bilirubin (µmol/L)

h in dia
te
200 Hig rme of severe hyperbilirubinemia (evidence level 1b). Testing for
i nte e
Low zon G6PD deficiency is advised in boys and girls at increased risk
Low
150
(eg, children of Mediterranean, Middle Eastern, African [17]
100
or Southeast Asian origin) (18,19). G6PD-deficient new-
borns require intervention at a lower TSB concentration (18);
50 therefore, a test for G6PD deficiency should be considered in
all infants with severe hyperbilirubinemia (evidence level 5)
0
0 12 24 36 48 60 72 84 96 108 120 132 144 (18). Unfortunately, in many centres, it currently takes several
Age (hours)
days for a G6PD deficiency screening test result to become
Figure 1) Nomogram for evaluation of screening total serum bilirubin available. Because G6PD deficiency is a disease with life-long
(TSB) concentration in term and late preterm infants, according to the implications, its identification is still of value for the infant.
TSB concentration obtained at a known postnatal age in hours. Plot the
TSB on this figure, then refer to Table 3 for action to be taken Recommendations
• All mothers should be tested for ABO and Rh (D)
blood types and be screened for red cell antibodies
Figure 1). Combining a timed TSB at less than 48 h of age during pregnancy (recommendation grade D [Table 2]).
with gestational age (14) improved the prediction of a • If the mother was not tested, cord blood from the infant
subsequent TSB concentration greater than 342 µmol/L should be sent for evaluation of the blood group and a
(evidence level 2b). DAT (Coombs test) (recommendation grade D).
• Blood group evaluation and a DAT should be performed
Blood group and Coombs testing
in infants with early jaundice or in the high
ABO isoimmunization may cause severe hyperbilirubine-
intermediate zone (Figure 1) of mothers of blood group
mia, most commonly in blood group A or B infants born to
O (recommendation grade B).
a mother of group O (15,16). It is therefore recommended
to perform a DAT in infants who are clinically jaundiced, or • Selected at-risk infants of Mediterranean, Middle Eastern,
in the high intermediate zone (Figure 1) of mothers who are African or Southeast Asian origin should be screened for
group O. G6PD deficiency (recommendation grade D).
The usual antenatal screen for a panel of red cell antibod- • A test for G6PD deficiency should be considered in all
ies occasionally identifies more infrequent antibodies that infants with severe hyperbilirubinemia
increase the risk of hemolysis. Infants may require further (recommendation grade D).

402 Paediatr Child Health Vol 12 No 5 May/June 2007

 CPS Statement: FN 2007-02

TABLE 2 450
Grades of recommendation
Infants at lower risk (> 38 wks and well)
Infants at medium risk (> 38 wks and risk factors or 35–37 6/7 wks and well)
400 Infants at higher risk (35–37 6/7 wks and risk factors)
A Consistent level 1 studies
B Consistent level 2 or 3 studies 350

C Level 4 studies

Bilirubin (µmol/L)
300

D Level 5 evidence, or troublingly inconsistent or 250

inconclusive studies of any level
200

150 It is an option to provide conventional phototherapy in hospital or at home at TSB

levels 35–50 µmol/L below those shown, but home phototherapy should not be used
in any infant with risk factors.

WHO SHOULD HAVE THEIR 100 Use total bilirubin. Do not subtract direct reacting or conjugated bilirubin.
Risk factors = isoimmune hemolytic disease, G6PD deficiency, asphyxia, respiratory
distress, significant lethargy, temperature instability, sepsis, acidosis.
BILIRUBIN CONCENTRATION MEASURED, 50 For well infants 35–37 6/7 wks can adjust TSB threshold around the medium risk line;
lower levels for infants closer to 35 wks gestations and higher levels for infants
WHEN AND HOW? 0
closer to 37 6/7 wks.

Clinical assessment of jaundice is inadequate for diagnosing 0 12 24 36 48 60 72 84 96 108 120 132 144 156 168

Postnatal age (hours)

hyperbilirubinemia, particularly in infants with darker skin
colour; only 50% of babies with a TSB concentration Figure 2) Guidelines for intensive phototherapy in infants of 35 or more
weeks’ (wk) gestation. These guidelines are based on limited evidence and
greater than 128 µmol/L appear jaundiced. The peak TSB the levels shown are approximations. Intensive phototherapy should be used
concentration usually occurs between three and five days of when the total serum bilirubin (TSB) concentration exceeds the line indi-
age, at which time the majority of babies have already been cated for each category. G6PD Glucose-6-phosphate dehydrogenase
discharged from hospital. Therefore, it is clear that at the
usual age of discharge, TSB concentrations in the high zone
(Figure 1) cannot be reliably detected by visual inspection, the first 24 h and again, at a minimum of 24 h to 48 h later.
especially in infants with darker skin colour. This should be performed by an individual competent in the
It is therefore recommended that either TSB or transcu- assessment of the newborn who can, if necessary, immediately
taneous bilirubin (TcB) concentration be measured in all obtain a TSB or TcB measurement and arrange treatment for
infants between 24 h and 72 h of life; if the infant does not the infant, whether in hospital or after discharge.
require immediate treatment, the results should be plotted
on the predictive nomogram to determine the risk of pro- Measurement of bilirubin
gression to severe hyperbilirubinemia. The TSB (or TcB) Estimation of TSB using capillary blood sampling is accept-
and the predictive zone should be recorded, a copy given to able (21,22). TcB measurements are also acceptable, however,
the family at the time of discharge and follow-up arrange- there are several limitations to TcB measurements – they
ments should be made for infants who are at elevated risk of become unreliable after initiation of phototherapy and may
developing severe hyperbilirubinemia. also be unreliable with changes in skin colour and thickness.
If the TSB concentration has not been measured earlier The results are more accurate at lower levels of bilirubin;
because of clinical jaundice, a TSB measurement should be therefore, the use of TcB as a screening device is reasonable.
obtained at the same time of the metabolic screening test to The available devices differ in accuracy; the safe use of TcB
decrease pain and minimize costs; alternatively a TcB meas- mandates knowledge of the accuracy of the individual
urement should be obtained either at discharge or before 72 h device. The 95% CIs for TSB based on the TcB concentra-
of life (14). tion range from approximately 37 µmol/L to 78 µmol/L
Some of the most severely affected infants require therapy (23,24). For example, if the 95% CI is 37 µmol/L, then a
initiation before the time of the screen; sudden increases in TcB concentration greater than 37 µmol/L below the inter-
TSB concentration may also occasionally occur after the first vention line (Figure 2) should be safe (eg, if the interven-
two to three days (20), particularly in association with exces- tion at 24 h is at 170 µmol/L, then a TcB concentration of
sive postnatal weight loss. Therefore, the institution of a pro- less than 133 µmol/L should be safe) (evidence level 1b).
gram of universal screening does not replace the need for
careful on-going assessment of newborn infants continuing Measurement of conjugated bilirubin
throughout the first weeks of life. Systems to ensure follow-up Early neonatal jaundice is generally due to unconjugated
within recommended intervals after hospital discharge must hyperbilirubinemia in infants placed on phototherapy; meas-
be in place so that an infant who develops severe hyperbiliru- urement of the conjugated fraction should be considered to
binemia can be identified and treated promptly. This requires, detect the uncommon case of an infant with an elevation.
for example, that an infant discharged from hospital within However, previous reports on the epidemiology of bilirubin
the first 24 h of life be reviewed within 24 h, any day of the toxicity use the TSB concentration as the standard, which
week, by an individual with the training to recognize neonatal remains the deciding value for phototherapy or other
hyperbilirubinemia, obtain measurement of TSB or TcB with- therapies. An infant with persistent jaundice (longer than two
out delay and refer the infant to a treatment facility if required. weeks) and/or hepatosplenomegaly should have an estimation
This individual may be from any medical or nursing discipline. of conjugated bilirubin fraction. A total conjugated bilirubin
In addition to universal measurement, all newborn infants concentration greater than 18 µmol/L or greater than 20% of
should be clinically assessed for jaundice repeatedly within the TSB concentration warrants further investigation (25).

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CPS Statement: FN 2007-02

Recommendations and experience in support of breastfeeding mothers (26)

• Either TSB or TcB concentration should be measured in (evidence level 5). Routine supplementation of breastfed
all infants during the first 72 h of life. If not required infants with water or dextrose water does not prevent
earlier because of clinical jaundice, TSB should be hyperbilirubinemia (evidence level 2b) (27).
obtained at the time of obtaining the metabolic
screening test; alternatively, a TcB measurement should Prevention of severe hyperbilirubinemia in infants with
be obtained either at discharge or, if not yet discharged, mild or moderate hyperbilirubinemia
before 72 h of life (recommendation grade C). Phototherapy
Phototherapy decreases the progression to severe hyper-
• If the TSB concentration does not require immediate
bilirubinemia in infants with moderate hyperbilirubinemia
intervention, the results should be plotted on the
(evidence level 1a). Its effectiveness is related to the area of
predictive nomogram. The results of the TSB
skin exposed and the intensity of the light at the skin at the
measurement, the time at which it was obtained and
relevant wavelengths (28). Intensity can be increased by
the zone should be recorded, and a copy given to the
using multiple phototherapy units (29) or moving the unit
parents. Follow-up of the infant should be
closer to the infant. Phototherapy causes minor increases in
individualized according to the risk assessment
transepidermal skin water loss in full-term infants. Side
(recommendation grade D).
effects include temperature instability, intestinal hyper-
• Any infant discharged before 24 h of life should be motility, interference with maternal-infant interaction and,
reviewed within 24 h by an individual with experience rarely, bronze discolouration of the skin. Phototherapy is
in the care of the newborn who has access to testing perceived by parents as implying that their infant’s jaundice
and treatment facilities (recommendation grade D). is a serious disease (30) (evidence level 2); reassurance of
• There should be a systematic approach to the risk the parents is an important part of their care. Eye patches
assessment of all infants before discharge and institution should be used to protect the developing retina (31).
of follow-up care if the infant develops jaundice Fluorescent light sources are most commonly used (32),
(recommendation grade D). but their intensity wanes over time; thus, a program of bio-
medical support for ensuring adequate light intensity is
• All newborn infants who are visibly jaundiced within important. Fibre optic phototherapy systems have the
the first 24 h of life should have a bilirubin level advantage of allowing the baby to be breastfed without
determined (recommendation grade D). interruption of phototherapy and eye pads are not required,
• Transcutaneous bilirubinometry is an acceptable but the disadvantage is that the peak intensity is lower than
method; the result should be summed with the 95% CI in fluorescent systems. Halogen spotlights may also be used,
of the device to estimate the maximum probable TSB but they must not be placed closer to the infant than the
concentration (recommendation grade C). manufacturer’s recommendation.
• TSB concentration may be estimated on either a capillary Intensive phototherapy, as recommended by the present
or a venous blood sample (recommendation grade C). position statement summary, implies that a high intensity of
light (greater than 30 µW/cm2/nm) is applied to the greatest
• Infants with severe or prolonged hyperbilirubinemia possible surface area of the infant. In usual clinical situations,
should be further investigated, including measurement this will imply two phototherapy units, or special high-
of the conjugated component of the bilirubin intensity fluorescent tubes, placed approximately 10 cm from
(recommendation grade C). the infant, who can be nursed in a bassinet. Usually the dia-
per can be left in place. In infants approaching the exchange
HOW CAN THE RISK OF SEVERE transfusion threshold, the addition of a fibre optic blanket
HYPERBILIRUBINEMIA BE REDUCED? under the infant can increase the surface area illuminated;
Primary prevention of severe hyperbilirubinemia the diaper should then be removed (or a phototherapy
Breastfeeding support wavelength-transmitting diaper used instead). The guide-
Although breastfed infants are at higher risk for developing lines for therapy (Figure 2) are based on limited direct evi-
severe hyperbilirubinemia than formula-fed infants, the dence, but are thought to be the most appropriate currently
known risks of acute bilirubin encephalopathy are very available standard. Conventional phototherapy – a single
small when weighed against the substantial known benefits bank of fluorescent lights placed above the incubator or
of breastfeeding (26). Support of the breastfeeding mother bassinet of an infant nursed with a diaper in place – is less
by knowledgeable individuals increases the frequency and effective because both surface area and intensity are reduced;
duration of breastfeeding, and providing such support is nevertheless, it will have some effect on TSB concentration.
recommended (evidence level 5). Exclusively breastfed Enteral feeding should be continued to replace missing
infants experience their maximum weight loss by day 3 and fluid, supply energy and reduce enterohepatic reuptake of
lose, on average, 6% to 8 % of their birth weight (26). the bilirubin (33).
Infants who lose more than 10% of their birth weight The recommendations for treatment are determined
should be carefully evaluated by an individual with training from Figure 2. These recommendations are as follows:

404 Paediatr Child Health Vol 12 No 5 May/June 2007

 CPS Statement: FN 2007-02

TABLE 3
Response to results of bilirubin screening
Greater than 37 weeks’ 35 to 37 6/7 weeks’ 35 to 37 6/7 weeks’
Zone gestation and DAT-negative gestation or DAT-positive gestation and DAT-positive
High Further testing or treatment required* Further testing or treatment required* Phototherapy required
High-intermediate Routine care Follow-up within 24 h to 48 h Further testing or treatment required*
Low-intermediate Routine care Routine care Further testing or treatment required*
Low Routine care Routine care Routine care
*Arrangements must be made for a timely (eg, within 24 h) re-evaluation of bilirubin by serum testing. Depending on the level indicated on Figure 2, treatment with
phototherapy may also be indicated. DAT Direct antiglobulin test

1. intensive phototherapy for infants with severe • Routine supplementation of breastfed infants with water
hyperbilirubinemia or those at greatly elevated risk of or dextrose water is not recommended (recommended
developing severe hyperbilirubinemia. grade B).
2. in addition, there is an option for conventional • Infants with a positive DAT who have predicted severe
phototherapy for those infants with moderately elevated disease based on antenatal investigation or an elevated
risk and at TSB concentrations of 35 µmol/L to 50 µmol/L risk of progressing to exchange transfusion based on the
below the thresholds (Figure 2). postnatal progression of TSB concentration should receive
A useful tool is available on-line at <http://bilitool.org> IVIG at a dose of 1 g/kg (recommended grade A).
for deciding whether intensive phototherapy would be recom- • A TSB concentration consistent with increased risk
mended by these guidelines. (Figure 1 and Table 3) should lead to enhanced surveil-
lance for the development of severe hyperbilirubinemia,
Interrupting breastfeeding
with follow-up within 24 h to 48 h, either in hospital or in
Interrupting breastfeeding as part of hyperbilirubinemia ther-
the community, and repeat estimation of TSB or TcB con-
apy is associated with an increase in the frequency of stopping
centration in most circumstances (recommended grade C).
breastfeeding by one month (evidence level 2b) (30). Contin-
uing breastfeeding in jaundiced infants receiving photothe- • Intensive phototherapy should be given according to the
rapy is not associated with adverse clinical outcomes (34). guidelines shown in Figure 2 (recommended grade D).
• Conventional phototherapy is an option at TSB concen-
Intravenous immunoglobulin
trations 35 µmol/L to 50 µmol/L, lower than the guide-
Intravenous immunoglobulin (IVIG) at a dose of either
lines in Figure 2 (recommended grade D).
500 mg/kg or 1 g/kg reduces bilirubin concentrations in
newborns with immune hemolytic jaundice (35,36) and • Breastfeeding should be continued during phototherapy
reduces the need for exchange transfusion (evidence level 1a). (recommended grade A).
These studies only included infants at high risk of requiring an • Supplemental fluids should be administered, orally or by
exchange transfusion. IVIG should therefore be given to intravenous infusion, in infants receiving phototherapy
infants with predicted severe disease based on antenatal who are at elevated risk of progressing to exchange trans-
investigation and to those with an elevated risk of progressing fusion (recommended grade A).
to exchange transfusion.
HOW SHOULD SEVERE HYPERBILIRUBINEMIA
Supplemental fluids
BE TREATED?
Nondehydrated infants with severe jaundice appear to have a Phototherapy
reduced risk of progressing to exchange transfusion if they An infant who presents with severe hyperbilirubinemia or
receive extra fluids, either intravenous or orally (37,38) dur- who progresses to severe hyperbilirubinemia despite initial
ing intensive phototherapy (evidence level 1b). There is a treatment should receive immediate intensive phototherapy.
concern that offering supplemental oral fluids may interfere Bilirubin concentration should be checked within 2 h to 6 h
with the eventual duration of breastfeeding (39,40) (evidence of initiation of treatment to confirm response.
level 2b). The frequency of exchange transfusion in the stud- Consideration of further therapy should commence and
ies supporting supplemental fluids, noted above, was very high preparations for exchange transfusion may be indicated.
(37). In breastfed infants, therefore, extra fluids are indicated Supplemental fluids are indicated, and IVIG should be
for, but should be restricted to, those infants with an elevated given in the DAT-positive infant.
risk of requiring exchange transfusion (evidence level 1b).
Exchange transfusion
Recommendations If phototherapy fails to control the rising bilirubin concen-
• A program for breastfeeding support should be instituted tration, exchange transfusion is indicated to lower TSB
in every facility where babies are delivered (recommenda- concentration. Exchange transfusion should be considered
tion grade D). when the TSB exceeds the thresholds on Figure 3 (despite

Paediatr Child Health Vol 12 No 5 May/June 2007 405

CPS Statement: FN 2007-02

500 Infants at lower risk (> 38 wks and well)

concentration starts to fall. Community services should
Infants at medium risk (> 38 wks and risk factors or 35–37 6/7 wks and well)
Infants at higher risk (35–37 6/7 wks and risk factors)
include breastfeeding support and access to TSB or TcB test-
450 ing. Infants with isoimmunization are at risk for severe ane-
mia after several weeks; it is suggested that a repeat
400
hemoglobin measurement be performed after two weeks if it
Bilirubin (µmol/L)

350
was low at discharge, and at four weeks if it was normal (evi-
dence level 5). Infants requiring exchange transfusion or
300 those who exhibit neurological abnormalities should be
referred to regional multidisciplinary follow-up programs.
250

Immediate exchange is recommended if infant shows signs of acute bilirubin
Neurosensory hearing loss is of particular importance in
200
encephalopathy (hypertonia, arching, retrocollis, opisthotonos, fever, high pitched cry).

Risk factors = isoimmune hemolytic disease, G6PD deficiency, asphyxia, respiratory infants with severe hyperbilirubinemia, and their hearing
distress, significant lethargy, temperature instability, sepsis, acidosis.

Use total bilirubin. Do not subtract direct reacting or conjugated bilirubin.

If infant is well and 35–37 6/7 wks (medium risk) can individualize levels
screen should include brainstem auditory evoked potentials.
for exchange based on actual gestational age.
150
0 12 24 36 48 60 72 84 96 108 120 132 144 156 168
Further investigations
Postnatal age (hours)
The occurrence of severe hyperbilirubinemia mandates an
Figure 3) Guidelines for exchange transfusion in infants of 35 or more investigation of the cause of hyperbilirubinemia.
weeks’ (wk) gestation. These guidelines are based on limited evidence and Investigations should include clinically pertinent history of
the levels shown are approximations. Exchange transfusions should be
used when the total serum bilirubin (TSB) concentration exceeds the line the baby and the mother, family history, description of the
indicated for each category. G6PD Glucose-6-phosphate dehydrogenase labour and delivery, and the infant’s clinical course. A phys-
ical examination should be supplemented by laboratory
investigations (conjugated and unconjugated bilirubin
levels; direct Coombs test; hemoglobin and hematocrit
adequate intensive phototherapy). Preparation of blood for
levels, and complete blood cell count including differential
exchange transfusion may take several hours, during which
count, blood smear and red cell morphology). Investigations
time intensive phototherapy and supplemental fluids
for sepsis should be performed if warranted by the clinical
should be used and IVIG (in case of isoimmunization). If an
situation.
infant presents for medical care and is already above the
exchange transfusion line, then immediate consultation Recommendations
with a referral centre is required. Repeat measurement of • Adequate follow-up should be ensured for all infants
the TSB concentration just before performance of the who are jaundiced (recommendation grade D).
exchange is reasonable, as long as therapy is not thereby
delayed. In this way, some exchange transfusions may be • Infants requiring intensive phototherapy should be
avoided. Exchange transfusion is a procedure with substan- investigated for determination of the cause of jaundice
tial morbidity that should only be performed in centres with (recommendation grade C).
the appropriate expertise under the supervision of an expe-
rienced neonatologist. CONCLUSION
An infant with clinical signs of acute bilirubin Severe hyperbilirubinemia in relatively healthy term or late
encephalopathy should have an immediate exchange trans- preterm newborns (greater than 35 weeks’ gestation)
fusion (evidence level 4). continues to carry the potential for complications from
acute bilirubin encephalopathy and chronic sequelae.
Recommendations Careful assessment of the risk factors involved, a systematic
• Infants with a TSB concentration above the thresholds approach to the detection and follow-up of jaundice with
(Figure 3) should have immediate intensive the appropriate laboratory investigations, along with
phototherapy, and should be referred for further judicious phototherapy and exchange transfusion when
investigation and preparation for exchange transfusion indicated, are all essential to avoid these complications.
(recommendation category B).
ACKNOWLEDGEMENTS: The full position statement was
• An infant with clinical signs of acute bilirubin reviewed by the Canadian Paediatric Society’s Community
encephalopathy should have an immediate exchange Paediatrics Committee and The College of Family Physicians of
transfusion (recommendation category D). Canada.

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FETUS AND NEWBORN COMMITTEE

Members: Drs Khalid Aziz, Department of Pediatrics (Neonatology), Janeway Children’s Health and Rehabilitation Centre, St John’s,
Newfoundland and Labrador (board representative 2000-2006); Keith J Barrington, Royal Victoria Hospital, Montreal, Quebec (chair); Joanne
Embree, University of Manitoba, Winnipeg, Manitoba (board representative); Haresh Kirpalani, Children’s Hospital – Hamilton HSC, Hamilton,
Ontario; Koravangattu Sankaran, Royal University Hospital, Saskatoon, Saskatchewan; Hilary Whyte, The Hospital for Sick Children, Toronto,
Ontario (sabbatical 2006-2007); Robin Whyte, IWK Health Centre, Halifax, Nova Scotia
Liaisons: Drs Dan Farine, Mount Sinai Hospital, Toronto, Ontario (Society of Obstetricians and Gynaecologists of Canada); David Keegan,
London, Ontario (College of Family Physicians of Canada, Maternity and Newborn Care Committee); Francine Lefebvre, Sainte-Justine UHC
(Canadian Paediatric Society, Neonatal-Perinatal Medicine Section); Catherine McCourt, Ottawa, Ontario (Public Health Agency of Canada,
Health Surveillance and Epidemiology); Ms Shahirose Premji, Hamilton Health Sciences Centre (Neonatal Nurses); Dr Alfonso Solimano, BC’s
Children’s Hospital, Vancouver, British Columbia (Canadian Paediatric Society, Neonatal-Perinatal Medicine Section, 2002–2006); Dr Ann Stark,
Texas Children’s Hospital, Houston, Texas, USA (American Academy of Pediatrics, Committee on Fetus and Newborn); Ms Amanda Symington,
Hamilton Health Sciences Centre – McMaster Site, Hamilton, Ontario (Neonatal Nurses, 1999–2006)
Principal authors: Drs Keith Barrington, Royal Victoria Hospital, Montreal, Quebec; Koravangattu Sankaran, Royal University Hospital,
Saskatoon, Saskatchewan

The recommendations in this statement do not indicate an exclusive course of treatment or procedure to be followed. Variations, taking
into account individual circumstances, may be appropriate. Internet addresses are current at time of publication.

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