CLINICAL PRACTICE GUIDELINE
Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation
Subcommittee on Hyperbilirubinemia
Jaundice occurs in most newborn infants. Most jaundice is benign,
but because of the potential toxicity of bilirubin, newborn
infants must be monitored to identify those who might develop
severe hyperbilirubinemia and, in rare cases, acute bilirubin
encephalopathy or kernicterus. The focus of this guideline is
to reduce the incidence of severe hyperbilirubinemia and bilirubin
encephalopathy while minimizing the risks of unintended harm
such as maternal anxiety, decreased breastfeeding, and unnecessary
costs or treatment. Although kernicterus should almost always
be preventable, cases continue to occur. These guidelines provide
a framework for the prevention and management of hyperbilirubinemia
in newborn infants of 35 or more weeks of gestation. In every
infant, we recommend that clinicians 1) promote and support
successful breastfeeding; 2) perform a systematic assessment
before discharge for the risk of severe hyperbilirubinemia;
3) provide early and focused follow-up based on the risk assessment;
and 4) when indicated, treat newborns with phototherapy or exchange
transfusion to prevent the development of severe hyperbilirubinemia
and, possibly, bilirubin encephalopathy (kernicterus).
Key Words: hyperbilirubinemia • newborn • kernicterus • bilirubin encephalopathy • phototherapy
Abbreviations: AAP, American Academy of Pediatrics • TSB, total serum bilirubin • TcB, transcutaneous bilirubin • G6PD, glucose-6-phosphate dehydrogenase • ETCOc, end-tidal carbon monoxide corrected for ambient carbon monoxide • B/A, bilirubin/albumin • UB, unbound bilirubin
In October 1994, the Provisional Committee for Quality Improvement
and Subcommittee on Hyperbilirubinemia of the American Academy
of Pediatrics (AAP) produced a practice parameter dealing with
the management of hyperbilirubinemia in the healthy term newborn.1
The current guideline represents a consensus of the committee
charged by the AAP with reviewing and updating the existing
guideline and is based on a careful review of the evidence,
including a comprehensive literature review by the New England
Medical Center Evidence-Based Practice Center.2
(See "An Evidence-Based
Review of Important Issues Concerning Neonatal Hyperbilirubinemia"3
for a description of the methodology, questions addressed, and
conclusions of this report.) This guideline is intended for
use by hospitals and pediatricians, neonatologists, family physicians,
physician assistants, and advanced practice nurses who treat
newborn infants in the hospital and as outpatients. A list of
frequently asked questions and answers for parents is available
in English and Spanish at www.aap.org/family/jaundicefaq.htm
|| DEFINITION OF RECOMMENDATIONS
The evidence-based approach to guideline development requires
that the evidence in support of a policy be identified, appraised,
and summarized and that an explicit link between evidence and
recommendations be defined. Evidence-based recommendations are
based on the quality of evidence and the balance of benefits
and harms that is anticipated when the recommendation is followed.
This guideline uses the definitions for quality of evidence
and balance of benefits and harms established by the AAP Steering
Committee on Quality Improvement Management.4
See Appendix 1
for these definitions.
The draft practice guideline underwent extensive peer review by committees and sections within the AAP, outside organizations, and other individuals identified by the subcommittee as experts in the field. Liaison representatives to the subcommittee were invited to distribute the draft to other representatives and committees within their specialty organizations. The resulting comments were reviewed by the subcommittee and, when appropriate, incorporated into the guideline.
|| BILIRUBIN ENCEPHALOPATHY AND KERNICTERUS
Although originally a pathologic diagnosis characterized by
bilirubin staining of the brainstem nuclei and cerebellum, the
term "kernicterus" has come to be used interchangeably with
both the acute and chronic findings of bilirubin encephalopathy.
Bilirubin encephalopathy describes the clinical central nervous
system findings caused by bilirubin toxicity to the basal ganglia
and various brainstem nuclei. To avoid confusion and encourage
greater consistency in the literature, the committee recommends
that in infants the term "acute bilirubin encephalopathy" be
used to describe the acute manifestations of bilirubin toxicity
seen in the first weeks after birth and that the term "kernicterus"
be reserved for the chronic and permanent clinical sequelae
of bilirubin toxicity.
See Appendix 1 for the clinical manifestations of acute bilirubin encephalopathy and kernicterus.
|| FOCUS OF GUIDELINE
The overall aim of this guideline is to promote an approach
that will reduce the frequency of severe neonatal hyperbilirubinemia
and bilirubin encephalopathy and minimize the risk of unintended
harm such as increased anxiety, decreased breastfeeding, or
unnecessary treatment for the general population and excessive
cost and waste. Recent reports of kernicterus indicate that
this condition, although rare, is still occurring.2,5–10
Analysis of these reported cases of kernicterus suggests that if health care personnel follow the recommendations listed in this guideline, kernicterus would be largely preventable.
These guidelines emphasize the importance of universal systematic assessment for the risk of severe hyperbilirubinemia, close follow-up, and prompt intervention when indicated. The recommendations apply to the care of infants at 35 or more weeks of gestation. These recommendations seek to further the aims defined by the Institute of Medicine as appropriate for health care:11 safety, effectiveness, efficiency, timeliness, patient-centeredness, and equity. They specifically emphasize the principles of patient safety and the key role of timeliness of interventions to prevent adverse outcomes resulting from neonatal hyperbilirubinemia.
The following are the key elements of the recommendations provided by this guideline. Clinicians should:
- Promote and support successful breastfeeding.
- Establish nursery protocols for the identification and evaluation of hyperbilirubinemia.
- Measure the total serum bilirubin (TSB) or transcutaneous bilirubin (TcB) level on infants jaundiced in the first 24 hours.
- Recognize that visual estimation of the degree of jaundice can lead to errors, particularly in darkly pigmented infants.
- Interpret all bilirubin levels according to the infant’s age in hours.
- Recognize that infants at less than 38 weeks’ gestation, particularly those who are breastfed, are at higher risk of developing hyperbilirubinemia and require closer surveillance and monitoring.
- Perform a systematic assessment on all infants before discharge for the risk of severe hyperbilirubinemia.
- Provide parents with written and verbal information about newborn jaundice.
- Provide appropriate follow-up based on the time of discharge and the risk assessment.
- Treat newborns, when indicated, with phototherapy or exchange transfusion.
|| PRIMARY PREVENTION
In numerous policy statements, the AAP recommends breastfeeding
for all healthy term and near-term newborns. This guideline
strongly supports this general recommendation.
RECOMMENDATION 1.0: Clinicians should advise mothers to nurse their infants at least 8 to 12 times per day for the first several days12 (evidence quality C: benefits exceed harms).
Poor caloric intake and/or dehydration associated with inadequate breastfeeding may contribute to the development of hyperbilirubinemia.6,13,14 Increasing the frequency of nursing decreases the likelihood of subsequent significant hyperbilirubinemia in breastfed infants.15–17 Providing appropriate support and advice to breastfeeding mothers increases the likelihood that breastfeeding will be successful.
Additional information on how to assess the adequacy of intake in a breastfed newborn is provided in Appendix 1.
RECOMMENDATION 1.1: The AAP recommends against routine supplementation of nondehydrated breastfed infants with water or dextrose water (evidence quality B and C: harms exceed benefits).
Supplementation with water or dextrose water will not prevent hyperbilirubinemia or decrease TSB levels.18,19
RECOMMENDATION 2.0: Clinicians should perform ongoing systematic assessments during the neonatal period for the risk of an infant developing severe hyperbilirubinemia
|| SECONDARY PREVENTION
RECOMMENDATION 2.1: All pregnant women should be tested for ABO and Rh (D) blood types and have a serum screen for unusual isoimmune antibodies (evidence quality B: benefits exceed harms).
RECOMMENDATION 2.1.1: If a mother has not had prenatal blood grouping or is Rh-negative, a direct antibody test (or Coombs’ test), blood type, and an Rh (D) type on the infant’s (cord) blood are strongly recommended (evidence quality B: benefits exceed harms).
RECOMMENDATION 2.1.2: If the maternal blood is group O, Rh-positive, it is an option to test the cord blood for the infant’s blood type and direct antibody test, but it is not required provided that there is appropriate surveillance, risk assessment before discharge, and follow-up20 (evidence quality C: benefits exceed harms).
RECOMMENDATION 2.2: Clinicians should ensure that all infants are routinely monitored for the development of jaundice, and nurseries should have established protocols for the assessment of jaundice. Jaundice should be assessed whenever the infant’s vital signs are measured but no less than every 8 to 12 hours (evidence quality D: benefits versus harms exceptional).
In newborn infants, jaundice can be detected by blanching the skin with digital pressure, revealing the underlying color of the skin and subcutaneous tissue. The assessment of jaundice must be performed in a well-lit room or, preferably, in daylight at a window. Jaundice is usually seen first in the face and progresses caudally to the trunk and extremities,21 but visual estimation of bilirubin levels from the degree of jaundice can lead to errors.22–24 In most infants with TSB levels of less than 15 mg/dL (257 µmol/L), noninvasive TcB-measurement devices can provide a valid estimate of the TSB level.2,25–29 See Appendix 1 for additional information on the clinical evaluation of jaundice and the use of TcB measurements.
RECOMMENDATION 2.2.1: Protocols for the assessment of jaundice should include the circumstances in which nursing staff can obtain a TcB level or order a TSB measurement (evidence quality D: benefits versus harms exceptional).
RECOMMENDATION 3.0: A TcB and/or TSB measurement should be performed on every infant who is jaundiced in the first 24 hours after birth (Fig 1 and Table 1)30 (evidence quality C: benefits exceed harms). The need for and timing of a repeat TcB or TSB measurement will depend on the zone in which the TSB falls (Fig 2),25,31 the age of the infant, and the evolution of the hyperbilirubinemia. Recommendations for TSB measurements after the age of 24 hours are provided in Fig 1 and Table 1.
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|Fig 2. Nomogram for designation of risk in 2840 well newborns at 36 or more weeks’ gestational age with birth weight of 2000 g or more or 35 or more weeks’ gestational age and birth weight of 2500 g or more based on the hour-specific serum bilirubin values. The serum bilirubin level was obtained before discharge, and the zone in which the value fell predicted the likelihood of a subsequent bilirubin level exceeding the 95th percentile (high-risk zone) as shown in Appendix 1, Table 4. Used with permission from Bhutani et al.31 See Appendix 1 for additional information about this nomogram, which should not be used to represent the natural history of neonatal hyperbilirubinemia.
See Appendix 1 for capillary versus venous bilirubin levels.
RECOMMENDATION 3.1: A TcB and/or TSB measurement should be performed if the jaundice appears excessive for the infant’s age (evidence quality D: benefits versus harms exceptional). If there is any doubt about the degree of jaundice, the TSB or TcB should be measured. Visual estimation of bilirubin levels from the degree of jaundice can lead to errors, particularly in darkly pigmented infants (evidence quality C: benefits exceed harms).
RECOMMENDATION 3.2: All bilirubin levels should be interpreted according to the infant’s age in hours (Fig 2) (evidence quality C: benefits exceed harms).
Cause of Jaundice
RECOMMENDATION 4.1: The possible cause of jaundice should be sought in an infant receiving phototherapy or whose TSB level is rising rapidly (ie, crossing percentiles [Fig 2]) and is not explained by the history and physical examination (evidence quality D: benefits versus harms exceptional).
RECOMMENDATION 4.1.1: Infants who have an elevation of direct-reacting or conjugated bilirubin should have a urinalysis and urine culture.32 Additional laboratory evaluation for sepsis should be performed if indicated by history and physical examination (evidence quality C: benefits exceed harms).
See Appendix 1 for definitions of abnormal levels of direct-reacting and conjugated bilirubin.
RECOMMENDATION 4.1.2: Sick infants and those who are jaundiced at or beyond 3 weeks should have a measurement of total and direct or conjugated bilirubin to identify cholestasis (Table 1) (evidence quality D: benefit versus harms exceptional). The results of the newborn thyroid and galactosemia screen should also be checked in these infants (evidence quality D: benefits versus harms exceptional).
RECOMMENDATION 4.1.3: If the direct-reacting or conjugated bilirubin level is elevated, additional evaluation for the causes of cholestasis is recommended (evidence quality C: benefits exceed harms).
RECOMMENDATION 4.1.4: Measurement of the glucose-6-phosphate dehydrogenase (G6PD) level is recommended for a jaundiced infant who is receiving phototherapy and whose family history or ethnic or geographic origin suggest the likelihood of G6PD deficiency or for an infant in whom the response to phototherapy is poor (Fig 3) (evidence quality C: benefits exceed harms).
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|Fig 3. Guidelines for phototherapy in hospitalized infants of 35 or more weeks’ gestation.
Note: These guidelines are based on limited evidence and the levels shown are approximations. The guidelines refer to the use of intensive phototherapy which should be used when the TSB exceeds the line indicated for each category. Infants are designated as "higher risk" because of the potential negative effects of the conditions listed on albumin binding of bilirubin,45–47 the blood-brain barrier,48 and the susceptibility of the brain cells to damage by bilirubin.48
"Intensive phototherapy" implies irradiance in the blue-green spectrum (wavelengths of approximately 430–490 nm) of at least 30 µW/cm2 per nm (measured at the infant’s skin directly below the center of the phototherapy unit) and delivered to as much of the infant’s surface area as possible. Note that irradiance measured below the center of the light source is much greater than that measured at the periphery. Measurements should be made with a radiometer specified by the manufacturer of the phototherapy system.
See Appendix 2 for additional information on measuring the dose of phototherapy, a description of intensive phototherapy, and of light sources used.
If total serum bilirubin levels approach or exceed the exchange transfusion line (Fig 4), the sides of the bassinet, incubator, or warmer should be lined with aluminum foil or white material.50 This will increase the surface area of the infant exposed and increase the efficacy of phototherapy.51 If the total serum bilirubin does not decrease or continues to rise in an infant who is receiving intensive phototherapy, this strongly suggests the presence of hemolysis.
Infants who receive phototherapy and have an elevated direct-reacting or conjugated bilirubin level (cholestatic jaundice) may develop the bronze-baby syndrome. See Appendix 2 for the use of phototherapy in these infants.
G6PD deficiency is widespread and frequently unrecognized, and although it is more common in the populations around the Mediterranean and in the Middle East, Arabian peninsula, Southeast Asia, and Africa, immigration and intermarriage have transformed G6PD deficiency into a global problem.33,34 Furthermore, G6PD deficiency occurs in 11% to 13% of African Americans, and kernicterus has occurred in some of these infants.5,33 In a recent report, G6PD deficiency was considered to be the cause of hyperbilirubinemia in 19 of 61 (31.5%) infants who developed kernicterus.5 (See Appendix 1 for additional information on G6PD deficiency.)
Risk Assessment Before Discharge
RECOMMENDATION 5.1: Before discharge, every newborn should be assessed for the risk of developing severe hyperbilirubinemia, and all nurseries should establish protocols for assessing this risk. Such assessment is particularly important in infants who are discharged before the age of 72 hours (evidence quality C: benefits exceed harms).
RECOMMENDATION 5.1.1: The AAP recommends 2 clinical options used individually or in combination for the systematic assessment of risk: predischarge measurement of the bilirubin level using TSB or TcB and/or assessment of clinical risk factors. Whether either or both options are used, appropriate follow-up after discharge is essential (evidence quality C: benefits exceed harms).
The best documented method for assessing the risk of subsequent hyperbilirubinemia is to measure the TSB or TcB level25,31,35–38 and plot the results on a nomogram (Fig 2). A TSB level can be obtained at the time of the routine metabolic screen, thus obviating the need for an additional blood sample. Some authors have suggested that a TSB measurement should be part of the routine screening of all newborns.5,31 An infant whose predischarge TSB is in the low-risk zone (Fig 2) is at very low risk of developing severe hyperbilirubinemia.5,38
Table 2 lists those factors that are clinically significant and most frequently associated with an increase in the risk of severe hyperbilirubinemia. But, because these risk factors are common and the risk of hyperbilirubinemia is small, individually the factors are of limited use as predictors of significant hyperbilirubinemia.39 Nevertheless, if no risk factors are present, the risk of severe hyperbilirubinemia is extremely low, and the more risk factors present, the greater the risk of severe hyperbilirubinemia.39 The important risk factors most frequently associated with severe hyperbilirubinemia are breastfeeding, gestation below 38 weeks, significant jaundice in a previous sibling, and jaundice noted before discharge.39,40 A formula-fed infant of 40 or more weeks’ gestation is at very low risk of developing severe hyperbilirubinemia.39
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|TABLE 2. Risk Factors for Development of Severe Hyperbilirubinemia in Infants of 35 or More Weeks’ Gestation (in Approximate Order of Importance)
Hospital Policies and Procedures
RECOMMENDATION 6.1: All hospitals should provide written and verbal information for parents at the time of discharge, which should include an explanation of jaundice, the need to monitor infants for jaundice, and advice on how monitoring should be done (evidence quality D: benefits versus harms exceptional).
An example of a parent-information handout is available in English and Spanish at www.aap.org/family/jaundicefaq.htm.
RECOMMENDATION 6.1.1: All infants should be examined by a qualified health care professional in the first few days after discharge to assess infant well-being and the presence or absence of jaundice. The timing and location of this assessment will be determined by the length of stay in the nursery, presence or absence of risk factors for hyperbilirubinemia (Table 2 and Fig 2), and risk of other neonatal problems (evidence quality C: benefits exceed harms).
Timing of Follow-up
RECOMMENDATION 6.1.2: Follow-up should be provided as follows:
||Should Be Seen by Age
|Before age 24 h
|Between 24 and 47.9 h
|Between 48 and 72 h
For some newborns discharged before 48 hours, 2 follow-up visits may be required, the first visit between 24 and 72 hours and the second between 72 and 120 hours. Clinical judgment should be used in determining follow-up. Earlier or more frequent follow-up should be provided for those who have risk factors for hyperbilirubinemia (Table 2), whereas those discharged with few or no risk factors can be seen after longer intervals (evidence quality C: benefits exceed harms).
RECOMMENDATION 6.1.3: If appropriate follow-up cannot be ensured in the presence of elevated risk for developing severe hyperbilirubinemia, it may be necessary to delay discharge either until appropriate follow-up can be ensured or the period of greatest risk has passed (72-96 hours) (evidence quality D: benefits versus harms exceptional).
RECOMMENDATION 6.1.4: The follow-up assessment should include the infant’s weight and percent change from birth weight, adequacy of intake, the pattern of voiding and stooling, and the presence or absence of jaundice (evidence quality C: benefits exceed harms). Clinical judgment should be used to determine the need for a bilirubin measurement. If there is any doubt about the degree of jaundice, the TSB or TcB level should be measured. Visual estimation of bilirubin levels can lead to errors, particularly in darkly pigmented infants (evidence quality C: benefits exceed harms).
See Appendix 1 for assessment of the adequacy of intake in breastfeeding infants.
Phototherapy and Exchange Transfusion
RECOMMENDATION 7.1: Recommendations for treatment are given in Table 3 and Figs 3 and 4 (evidence quality C: benefits exceed harms). If the TSB does not fall or continues to rise despite intensive phototherapy, it is very likely that hemolysis is occurring. The committee’s recommendations for discontinuing phototherapy can be found in Appendix 2
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|TABLE 3. Example of a Clinical Pathway for Management of the Newborn Infant Readmitted for Phototherapy or Exchange Transfusion
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|Fig 4. Guidelines for exchange transfusion in infants 35 or more weeks’ gestation.
Note that these suggested levels represent a consensus of most of the committee but are based on limited evidence, and the levels shown are approximations. See ref. 3 for risks and complications of exchange transfusion. During birth hospitalization, exchange transfusion is recommended if the TSB rises to these levels despite intensive phototherapy. For readmitted infants, if the TSB level is above the exchange level, repeat TSB measurement every 2 to 3 hours and consider exchange if the TSB remains above the levels indicated after intensive phototherapy for 6 hours.
The following B/A ratios can be used together with but in not in lieu of the TSB level as an additional factor in determining the need for exchange transfusion52:
||B/A Ratio at Which Exchange Transfusion Should be Considered
|TSB µmol/L/Alb, µmol/L
|Infants 38 0/7 wk
|Infants 35 0/7–36 6/7 wk and well or 38 0/7 wk if higher risk or isoimmune hemolytic disease or G6PD deficiency
|Infants 35 0/7–37 6/7 wk if higher risk or isoimmune hemolytic disease or G6PD deficiency
If the TSB is at or approaching the exchange level, send blood for immediate type and crossmatch. Blood for exchange transfusion is modified whole blood (red cells and plasma) crossmatched against the mother and compatible with the infant.53
RECOMMENDATION 7.1.1: In using the guidelines for phototherapy and exchange transfusion (Figs 3 and 4), the direct-reacting (or conjugated) bilirubin level should not be subtracted from the total (evidence quality D: benefits versus harms exceptional).
In unusual situations in which the direct bilirubin level is 50% or more of the total bilirubin, there are no good data to provide guidance for therapy, and consultation with an expert in the field is recommended.
RECOMMENDATION 7.1.2: If the TSB is at a level at which exchange transfusion is recommended (Fig 4) or if the TSB level is 25 mg/dL (428 µmol/L) or higher at any time, it is a medical emergency and the infant should be admitted immediately and directly to a hospital pediatric service for intensive phototherapy. These infants should not be referred to the emergency department, because it delays the initiation of treatment54 (evidence quality C: benefits exceed harms).
RECOMMENDATION 7.1.3: Exchange transfusions should be performed only by trained personnel in a neonatal intensive care unit with full monitoring and resuscitation capabilities (evidence quality D: benefits versus harms exceptional).
RECOMMENDATION 7.1.4: In isoimmune hemolytic disease, administration of intravenous -globulin (0.5-1 g/kg over 2 hours) is recommended if the TSB is rising despite intensive phototherapy or the TSB level is within 2 to 3 mg/dL (34-51 µmol/L) of the exchange level (Fig 4).55 If necessary, this dose can be repeated in 12 hours (evidence quality B: benefits exceed harms).
Intravenous -globulin has been shown to reduce the need for exchange transfusions in Rh and ABO hemolytic disease.55–58 Although data are limited, it is reasonable to assume that intravenous -globulin will also be helpful in the other types of Rh hemolytic disease such as anti-C and anti-E.
Serum Albumin Levels and the Bilirubin/Albumin Ratio
RECOMMENDATION 7.1.5: It is an option to measure the serum albumin level and consider an albumin level of less than 3.0 g/dL as one risk factor for lowering the threshold for phototherapy use (see Fig 3) (evidence quality D: benefits versus risks exceptional.).
RECOMMENDATION 7.1.6: If an exchange transfusion is being considered, the serum albumin level should be measured and the bilirubin/albumin (B/A) ratio used in conjunction with the TSB level and other factors in determining the need for exchange transfusion (see Fig 4) (evidence quality D: benefits versus harms exceptional).
The recommendations shown above for treating hyperbilirubinemia are based primarily on TSB levels and other factors that affect the risk of bilirubin encephalopathy. This risk might be increased by a prolonged (rather than a brief) exposure to a certain TSB level.59,60 Because the published data that address this issue are limited, however, it is not possible to provide specific recommendations for intervention based on the duration of hyperbilirubinemia.
See Appendix 1 for the basis for recommendations 7.1 through 7.1.6 and for the recommendations provided in Figs 3 and 4. Appendix 1 also contains a discussion of the risks of exchange transfusion and the use of B/A binding.
Acute Bilirubin Encephalopathy
RECOMMENDATION 7.1.7: Immediate exchange transfusion is recommended in any infant who is jaundiced and manifests the signs of the intermediate to advanced stages of acute bilirubin encephalopathy61,62 (hypertonia, arching, retrocollis, opisthotonos, fever, high-pitched cry) even if the TSB is falling (evidence quality D: benefits versus risks exceptional).
RECOMMENDATION 7.2: All nurseries and services treating infants should have the necessary equipment to provide intensive phototherapy (see Appendix 2) (evidence quality D: benefits exceed risks).
Outpatient Management of the Jaundiced Breastfed Infant
RECOMMENDATION 7.3: In breastfed infants who require phototherapy (Fig 3), the AAP recommends that, if possible, breastfeeding should be continued (evidence quality C: benefits exceed harms). It is also an option to interrupt temporarily breastfeeding and substitute formula. This can reduce bilirubin levels and/or enhance the efficacy of phototherapy63–65 (evidence quality B: benefits exceed harms). In breastfed infants receiving phototherapy, supplementation with expressed breast milk or formula is appropriate if the infant’s intake seems inadequate, weight loss is excessive, or the infant seems dehydrated.
|| IMPLEMENTATION STRATEGIES
The Institute of Medicine11
recommends a dramatic change in
the way the US health care system ensures the safety of patients.
The perspective of safety as a purely individual responsibility
must be replaced by the concept of safety as a property of systems.
Safe systems are characterized by a shared knowledge of the
goal, a culture emphasizing safety, the ability of each person
within the system to act in a manner that promotes safety, minimizing
the use of memory, and emphasizing the use of standard procedures
(such as checklists), and the involvement of patients/families
as partners in the process of care.
These principles can be applied to the challenge of preventing severe hyperbilirubinemia and kernicterus. A systematic approach to the implementation of these guidelines should result in greater safety. Such approaches might include
- The establishment of standing protocols for nursing assessment of jaundice, including testing TcB and TSB levels, without requiring physician orders.
- Checklists or reminders associated with risk factors, age at discharge, and laboratory test results that provide guidance for appropriate follow-up.
- Explicit educational materials for parents (a key component of all AAP guidelines) concerning the identification of newborns with jaundice.
Epidemiology of Bilirubin-Induced Central Nervous System Damage
|| FUTURE RESEARCH
There is a need for appropriate epidemiologic data to document
the incidence of kernicterus in the newborn population, the
incidence of other adverse effects attributable to hyperbilirubinemia
and its management, and the number of infants whose TSB levels
exceed 25 or 30 mg/dL (428-513 µmol/L). Organizations
such as the Centers for Disease Control and Prevention should
implement strategies for appropriate data gathering to identify
the number of infants who develop serum bilirubin levels above
25 or 30 mg/dL (428-513 µmol/L) and those who develop
acute and chronic bilirubin encephalopathy. This information
will help to identify the magnitude of the problem; the number
of infants who need to be screened and treated to prevent 1
case of kernicterus; and the risks, costs, and benefits of different
strategies for prevention and treatment of hyperbilirubinemia.
In the absence of these data, recommendations for intervention
cannot be considered definitive.
Effect of Bilirubin on the Central Nervous System
The serum bilirubin level by itself, except when it is extremely high and associated with bilirubin encephalopathy, is an imprecise indicator of long-term neurodevelopmental outcome.2 Additional studies are needed on the relationship between central nervous system damage and the duration of hyperbilirubinemia, the binding of bilirubin to albumin, and changes seen in the brainstem auditory evoked response. These studies could help to better identify risk, clarify the effect of bilirubin on the central nervous system, and guide intervention.
Identification of Hemolysis
Because of their poor specificity and sensitivity, the standard laboratory tests for hemolysis (Table 1) are frequently unhelpful.66,67 However, end-tidal carbon monoxide, corrected for ambient carbon monoxide (ETCOc), levels can confirm the presence or absence of hemolysis, and measurement of ETCOc is the only clinical test that provides a direct measurement of the rate of heme catabolism and the rate of bilirubin production.68,69 Thus, ETCOc may be helpful in determining the degree of surveillance needed and the timing of intervention. It is not yet known, however, how ETCOc measurements will affect management.
Nomograms and the Measurement of Serum and TcB
It would be useful to develop an age-specific (by hour) nomogram for TSB in populations of newborns that differ with regard to risk factors for hyperbilirubinemia. There is also an urgent need to improve the precision and accuracy of the measurement of TSB in the clinical laboratory.70,71 Additional studies are also needed to develop and validate noninvasive (transcutaneous) measurements of serum bilirubin and to understand the factors that affect these measurements. These studies should also assess the cost-effectiveness and reproducibility of TcB measurements in clinical practice.2
There is now evidence that hyperbilirubinemia can be effectively prevented or treated with tin-mesoporphyrin,72–75 a drug that inhibits the production of heme oxygenase. Tin-mesoporphyrin is not approved by the US Food and Drug Administration. If approved, tin-mesoporphyrin could find immediate application in preventing the need for exchange transfusion in infants who are not responding to phototherapy.75
Dissemination and Monitoring
Research should be directed toward methods for disseminating the information contained in this guideline to increase awareness on the part of physicians, residents, nurses, and parents concerning the issues of neonatal hyperbilirubinemia and strategies for its management. In addition, monitoring systems should be established to identify the impact of these guidelines on the incidence of acute bilirubin encephalopathy and kernicterus and the use of phototherapy and exchange transfusions.
Kernicterus is still occurring but should be largely preventable
if health care personnel follow the recommendations listed in
this guideline. These recommendations emphasize the importance
of universal, systematic assessment for the risk of severe hyperbilirubinemia,
close follow-up, and prompt intervention, when necessary.