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Research

Incidence and causes of severe neonatal hyperbilirubinemia in Canada

Michael Sgro, Douglas Campbell and Vibhuti Shah
CMAJ September 12, 2006 175 (6) 587-590; DOI: https://doi.org/10.1503/cmaj.060328
Michael Sgro
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Douglas Campbell
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Vibhuti Shah
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  • Coomb's testing and neonatal hyperbilirubinemia
    Douglas M Campbell
    Posted on: 22 December 2006
  • Management of Neonatal Hyperbilirubinemia
    Michael D Sgro
    Posted on: 18 October 2006
  • Use of the Coombs� test in the investigation of neonatal hyperbilirubinemia
    Stephen Wainer
    Posted on: 11 October 2006
  • Posted on: (22 December 2006)
    Coomb's testing and neonatal hyperbilirubinemia
    • Douglas M Campbell

    Dr. Bruce Squires Editor Emeritus Canadian Medical Association Journal 1867 Alta Vista Drive Ottawa, Ontario K1G 3Y6

    1. Sgro M, Campbell D, Shah V. Incidence and causes of severe hyperbilirubinemia in Canada. CMAJ 2006;175(6):587-90. 2. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004;114:297-316...

    Show More

    Dr. Bruce Squires Editor Emeritus Canadian Medical Association Journal 1867 Alta Vista Drive Ottawa, Ontario K1G 3Y6

    1. Sgro M, Campbell D, Shah V. Incidence and causes of severe hyperbilirubinemia in Canada. CMAJ 2006;175(6):587-90. 2. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004;114:297-316. 3. Fetus and Newborn Committee, Canadian Paediatric Society. Approach to the management of hyperbilirubinemia in term newborn infants. Paediatr Child Health 1999;4(2):161-164. 4. Engle WD, Jackson GL, Stehel EK, et al. Evaluation of a transcutaneous jaundice meter following hospital discharge in term and near-term neonates. J Perinatology 2005;25:486-90. 5. Danayan KC, Sgro M, McGovern V, et al. Transcutatneous Bilirubin Measurement in jaundiced newborns. Paediatr Child Health 2006;11(supplement B):26B. 6. Suresh GK, Clark RE. Cost-effectivenes of strategies that are intended to prevent kernicterus in newborn infants. Pediatrics 2004;114;917-24.

    Dear Dr. Squires:

    DOI:10.1503/cmaj.060328

    We thank Dr. Wainer and colleagues for their comments regarding our recent article (1). We agree that any test in isolation, including Coomb’s testing, is not the most effective way of identifying infants at risk of neonatal hyperbilirubinemia. Our recommendation for Coomb’s testing was not for all infants with mothers of blood type O+, only those who had identified risk factors for hyperbilirubinemia or were already jaundiced at the time of discharge.

    Despite existing guidelines both by the AAP (2) and CPS (3) which recommends identification of risk, and close follow-up of these infants, our data clearly demonstrates that severe neonatal hyperbilirubinemia continues to exist in alarming numbers in Canada. The most common cause in our population was ABO incompatibility and this needs to be emphasized to pediatricians and primary health care practitioners.

    In terms of cost-effectiveness, many strategies have been postulated as ‘effective’ in preventing severe neonatal hyperbilirubinemia. We welcome the use of strategies coupling clinical suspicion of risk of hyperbilirubinemia at the time of discharge, with close out-patient monitoring. Transcutaneous bilirubinometers, while very useful within a clinical context, may not always serve as a substitute for a serum bilirubin at levels at which phototherapy is required (4, 5). No reported strategies have yet been proven to be cost-effective (6). This is largely because of the unanswered question of prevalence of long-term neurological sequelae of severe hyperbilirubinemia. Only when a population is studied systematically can this issue be properly addressed.

    Michael Sgro Douglas Campbell Department of Pediatrics St. Michael's Hospital Toronto, Ont. Vibhuti Shah Mount Sinai Department of Pediatrics Toronto, Ont.

    Conflict of Interest:

    None declared

    Show Less
    Competing Interests: None declared.
  • Posted on: (18 October 2006)
    Management of Neonatal Hyperbilirubinemia
    • Michael D Sgro

    Maisels and Newman’s commentary (CMAJ 2006;175:599) accurately pointed out some difficulties in interpretation of data from our recent article1. There is no doubt that due to the inherent nature in which studies are conducted through surveillance programs incompleteness of data collection can lead to an underestimation of the number of index cases and limit our ability to thoroughly analyze the underlying etiologies. Des...

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    Maisels and Newman’s commentary (CMAJ 2006;175:599) accurately pointed out some difficulties in interpretation of data from our recent article1. There is no doubt that due to the inherent nature in which studies are conducted through surveillance programs incompleteness of data collection can lead to an underestimation of the number of index cases and limit our ability to thoroughly analyze the underlying etiologies. Despite these limitations, our study has shown that severe hyperbilirubinemia continues to occur in Canada and that the majority of infants that were discharged home were subsequently readmitted shortly after leaving the hospital. This raises the concern that at the time of initial discharge health care providers are missing an opportunity to prevent severe hyperbilirubinemia. Although recommendations from the AAP2 have recently been published, they are currently not being followed or are impractical to apply for these patients.

    Introducing routine screening tests (serum bilirubin, blood group and Coombs’ testing) in order to prevent severe hyperbilirubinemia may have financial implications including longer hospital stays for neonates. Given the impact of introducing these investigations, it is of paramount importance to understand the burden of illness that severe hyperbilirubinemia and its complications cause in Canada, namely bilirubin -induced neurological dysfunction (BIND) and kernicterus. Newman and Maisels state that kernicterus is estimated to be infrequent, anywhere from 1:100,000 to 1:50,000 live births. They acknowledge however that this is based on very little research data. They reference a Danish study3 that estimated the incidence of kernicterus at 1:50,000 to 1:60,000. It is important to note that this was by no means a systematic review of their population, and was based on case reports in a relatively homogenous population. In our study 50.4% of the infants reported were born to non- caucasian mothers1. Ethnicity may be one of the contributing factor responsible for severe hyperbilirubinemia secondary to a higher incidence of Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency in these populations and a delay in recognition of jaundice due to the babies darker pigmentation.

    We believe that careful assessment of newborns at the time of discharge is helpful, and consideration of blood group incompatibility and risk of G6PD deficiency would be helpful in planning investigations prior to discharge such as serum bilirubin as well as appropriate follow-up in order to prevent neonatal hyperbilirubinemia, readmission to hospital and possible neurological complications. A more accurate estimate of kernicterus is of paramount importance in order to justify cord blood testing and the measurement of serum bilirubin at the time an infant is discharged from hospital.

    REFERENCES 1. Sgro M, Campbell DM, Shah V. Incidence and causes of severe neonatal hyperbilirubinemia in Canada. CMAJ 2006;175(6):587-90. 2. American Academy of Pediatrics Clinical practice guideline: management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004;114(1):297-316. 3. Ebbesen F. Recurrence of kernicterus in term and near-term infants in Denmark. Acta Paediatr 2000;89(10):1213-7.

    Michael Sgro Douglas Campbell Department of Pediatrics St. Michael's Hospital Toronto, Ont. Vibhuti Shah Mount Sinai Department of Pediatrics Toronto, Ont.

    Conflict of Interest:

    None declared

    Show Less
    Competing Interests: None declared.
  • Posted on: (11 October 2006)
    Use of the Coombs� test in the investigation of neonatal hyperbilirubinemia
    • Stephen Wainer

     

    5 October 2006

     

     

    The Editor

    CMAJ

     

     

     

    Use of the Coombs’ test in the investigation of neonatal hyperbilirubinemia

     

    ...
    Show More

     

    5 October 2006

     

     

    The Editor

    CMAJ

     

     

     

    Use of the Coombs’ test in the investigation of neonatal hyperbilirubinemia

     

    While we fully support Dr Sgro and colleagues regarding the need for early identification and effective management of neonatal hyperbilirubinemia we were surprised to see their recommendations regarding the use of the Coombs’ test as a screening test for hyperbilirubinemia for all infants born to group O mothers.[1]

     

    The Coombs’ or direct antibody test (DAT) is a diagnostic test for the presence of antibodies bound to red cells in circulation. While the DAT is an important test when trying to identify the possible “cause” for neonatal hyperbilirubinemia it has very doubtful credentials when it comes to the prediction of hyperbilirubinemia.

    The following recent studies have examined the role of the DAT in predicting the development of significant hyperbilirubinemia (Table). As can be seen, the DAT has extremely limited usefulness as a screening test with low sensitivity and positive predictive values.

     

    Table:

     

    PPV (%)

    NPV (%)

    Sensitivity

    Specificity

    Meberg and Johansen[2]

    12

    96

    64

    65

    Herschel et al*[3]

    53

    89

    15

    98

    Dinesh‡[4]

    23

    92

    15

    95

    PPV = Positive Predictive Value

    NPV = Negative Predictive Value

    *Results for infants born to non-smoking mothers

    ‡ Calculated results from data based on need for phototherapy

     

    While the DAT is often assumed to reliably identify the presence of hemolysis, Herschel found that in comparison to end-tidal carbon monoxide concentration, the DAT showed only 8.5% sensitivity, 97.6% specificity and a positive predictive value of 25% for the detection of hemolysis in neonates. 3

     

    In addition to having very low predictive ability, the DAT is costly when used as a screening test. US studies looking at the costs of evaluating neonatal jaundice have reported the charge per test to be $17 - $47 (US).2,[5], [6], Newman and colleagues have examined the costs and benefits of investigating hyperbilirubinemia and concluded that this should be done on a case by case basis with more aggressive investigation of infants with early onset or severe hyperbilirubinemia.6 Holtzman has also stressed the need for critical appraisal of strategies intended to identify infants with hyperbilirubinemia.[7]

     

    In Calgary, routine DAT testing is being phased out in favour of a comprehensive hospital and community-based transcutaneous bilirubinometry (TcB) program. The reliability of TcB has been well documented and we believe that it provides a convenient, rapid, painless, cost-effective, and accurate screening assessment for hyperbilirubinemia in the term and near-term neonate, particularly when incorporated into routine Public Health Nurse well-baby visits.[8][9]

     

    In conclusion we believe that money is not well spent on routine DAT testing for all infants born to group O mothers and that the DAT should instead be reserved for diagnostic purposes in the child with early or clinically significant hyperbilirubinemia. A cost –effective “system based” approach to the timely and accurate identification of hyperbilirubinemia is, in our opinion, a more supportable strategy. Effective implementation of such a program should minimize the risk of bilirubin induced neurologic dysfunction or kernicterus.in the term or near-term infant[10]

     

     

    Sincerely,

     

     

    Stephen Wainer

    Paediatrician

    Assistant Clinical Professor, Department of Pediatrics, University of Calgary

    Regional Phototherapy Program

    Peter Lougheed Centre, Calgary.

     

     

    Jack Rabi

    Neonatologist

    Assistant Professor, University of Calgary Dept. of Pediatrics

     

     

     

    Martha Lyon

    Section Head, Pediatric & Neonatal Clinical Biochemistry

    Calgary Laboratory Services, Alberta Children's Hospital

     

     



    References:

    [1] Sgro M, Campbell D, Shah V. Incidence and causes of severe hyperbilirubinemia in Canada. CMAJ 2006;175(6):587-90.

    [2] Meberg A, Johansen KB. Screening for neonatal hyperbilirubinemia and ABO alloimunization at the time of testing for phenylketonuria and congenital hypothyreosis. Acta Paediatr 1998;87:1269-74.

    [3] Herschel M, et al. Evaluation of the Direct Antiglobulin (Coombs’) Test for identifying newborns at risk for hemolysis as determined by end-tidal carbon monoxide concentration (ETCOc); and comparison of the Coombs’ Test with ETCOc for detecting significant jaundice. J Perinatol 2002;22:341-47.

    [4] Dinesh D. Review of positive direct antiglobulin tests found on cord blood sampling. J Paediatr Child Health 2005;41(9-10):504-07.

    [5] Suresh Gk, Clark RE. Cost-effectiveness of strategies that are intended to prevent kernicterus in newborn infants. Pediatrics 2004;114;917-24

    [6] Newman TB, et al. Laboratory Evaluation of Jaundice in Newborns: Frequency, cost and yield. AJDC 1990;144:364-68.

    [7] Holtzman NA. Management of hyperbilirubinemia: quality of evidence and cost. Pediatrics 2004;114:1086-88.

    [8] Maisels MJ, Ostrea EM, Touch S, et al. Evaluation of a new transcutaneous bilirubinometer Pediatrics 2004;113:1628 –35.

    [9]Engle WD, Jackson GL, Stehel EK, et al. Evaluation of a transcutaneous jaundice meter following hospital discharge in term and near-term neonates. J Perinatol 2005;25:486-90.

    [10] Johnson LH, Bhutani VK. System-based approach to management of neonatal jaundice and prevention of kernicterus. J Pediatr 2002;140:396-403.

    Conflict of Interest:

    None declared

    Show Less
    Competing Interests: None declared.
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Canadian Medical Association Journal: 175 (6)
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Vol. 175, Issue 6
12 Sep 2006
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Incidence and causes of severe neonatal hyperbilirubinemia in Canada
Michael Sgro, Douglas Campbell, Vibhuti Shah
CMAJ Sep 2006, 175 (6) 587-590; DOI: 10.1503/cmaj.060328

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Incidence and causes of severe neonatal hyperbilirubinemia in Canada
Michael Sgro, Douglas Campbell, Vibhuti Shah
CMAJ Sep 2006, 175 (6) 587-590; DOI: 10.1503/cmaj.060328
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