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Kernicterus: Epidemiological Strategies for Its Prevention through Systems-

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Special Feature
Kernicterus: Epidemiological Strategies for Its Prevention
through Systems-Based Approaches
Vinod K. Bhutani, MD, FAAP
Lois H. Johnson, MD, FAAP
M. Jeffrey Maisels, MB, BCh, FAAP
Thomas B. Newman, MD, MPH
Ciaran Phibbs, PhD
Ann R. Stark, MD, FAAP
Marshalyn Yeargin-Allsopp, MD, APP
Kernicterus, thought to be due to severe hyperbilirubinemia, is an
uncommon disorder with tragic consequences, especially when it affects
healthy term and near-term infants. Early identification, prevention and
treatment of severe hyperbilirubinemia should make kernicterus a
preventable disease. However, national epidemiologic data are needed to
monitor any preventive strategies. Recommendations are provided to obtain
prospective data on the prevalence and incidence of severe
hyperbilirubinemia and associate mortality and neurologic injury using
standardized definitions, explore the clinical characteristics and root causes
of kernicterus in children identified in the Kernicterus Pilot Registry,
identify and test an indicator for population surveillance, validating
systems-based approaches to the management of newborn jaundice, and
explore the feasibility of using biologic or genetic markers to identify infants
at risk for hyperbilirubinemia. Increased knowledge about the incidence
and consequences of severe hyperbilirubinemia is essential to the planning,
implementation and assessment of interventions to ensure that infants
discharged as healthy from their birth hospitals have a safer transition to
home, avoiding morbidity due to hyperbilirubinemia and other disorders.
Department of Pediatrics(V.K.B.), University of Pennsylvania, Philadelphia, PA, USA;
Pennsylvania Hospital (L.H.J), University of Pennsylvania, Philadelphia, PA, USA; William
Beaumont Hospital (M.J.M.), Royal Oak, MI, USA; Departments of Epidemiology and Biostatistics
and Pediatrics (T.B.N.), University of California, San Francisco, CA, USA; Health Economics
Resource Center (C.P), Veterans Affairs Palo Alto Health Care System, Department of Health
Research and Policy, and Center for Primary Care and Outcomes Research, Stanford University
School of Medicine, Stanford, USA; Department of Newborn Medicine (A.R.S.), Brigham and
Women’s Hospital, Harvard Medical School, Boston, MA, USA; and National Center on Birth
Defects and Developmental Disabilities (M. Y.-A.), Centers for Disease Control and Prevention,
Atlanta, GA, USA.
Presented in part at the NICHD Conference, Research on Prevention of Bilirubin-Induced Brain
Injury and Kernicterus-From Bench to Bedside, at Bethesda, Md, USA, June 2003.
Address correspondence and reprint requests to Vinod K. Bhutani, MD, FAAP, Center for Research
on Reproduction and Women’s Health, 1315, BRB II/III, 421 Curie Blvd, University of
Pennsylvania, Philadelphia, PA 19140, USA.
650
At a recent NIHCD-sponsored conference, key questions were raised about
kernicterus and the need for additional strategies for its prevention. These
questions and an approach to their answers form the basis of this report.
Journal of Perinatology (2004) 24, 650–662. doi:10.1038/sj.jp.7211152
Published online 15 July 2004
A. IS KERNICTERUS A MATTER OF PUBLIC HEALTH
CONCERN?
Available Evidence
Kernicterus has long been recognized as the pathologic sequela of
severe hyperbilirubinemia. Although the condition is uncommon, the
consequences are tragic, especially when it affects otherwise healthy
term and near-term infants.1–5 Kernicterus has become uncommon
because of effective screening for and prevention of Rh
incompatibility, a historically important cause, and the accessibility of
phototherapy to treat hyperbilirubinemia due to increased production
and/or decreased elimination of bilirubin. Furthermore, adherence by
clinicians to the guidelines from the American Academy of Pediatrics
(AAP) concerning management of neonatal jaundice was expected to
eliminate severe hyperbilirubinemia and prevent kernicterus.6,7
Little contemporary information is available on the incidence or
prevalence of kernicterus or its consequences. In the reports from the
Pilot Kernicterus Registry and the Northern California Kaiser
Permanente Medical Care Program (KPMCP) database, neonatal
deaths due to kernicterus were ascertained from diagnostic codes on
death certificates. Limitations of such observations include the
retrospective design and possible under-reporting, delayed diagnosis,
or errors in coding. For example, it is not feasible to estimate
accurately a national incidence of kernicterus using the ICD-9 codes
773.4 and 747.7 for this diagnosis to query the HCUP database
(Healthcare Cost and Utilization Project Agency for Healthcare
Research and Quality, Rockville, MD; http://www.ahrq.gov/data/
hcup/hcupnet.htm) because the accuracy for annual reports is ±70
cases. That kernicterus occurs is evident from 125 cases of infants
who had been discharged as healthy from their birthing hospitals
that were voluntarily reported from 1992 to 2002 to the Pilot
Kernicterus Registry.1–5,8,9 In contrast, no cases of kernicterus in
infants with cerebral palsy were found in the retrospective database of
KPMCP during a similar time period (1991 to 1998).10 In addition,
among these 111,009 infants in the KPMCP database, 11 (0.01%)
developed total serum bilirubin (TSB) levels Z30 mg/dl, and none
of them apparently developed kernicterus.10 However, it is unclear
Journal of Perinatology 2004; 24:650–662
r 2004 Nature Publishing Group All rights reserved. 0743-8346/04 $30
www.nature.com/jp
Epidemiologic and Systems-Based Perspectives on Kernicterus Bhutani et al.

whether all cases were identified, since TSB was not routinely hospitalization (predominantly for jaundice from 14 studies listed
measured in all infants nor were these infants followed prospectively. in Table 2) range from 1.7 to 30.2 per 1000 live-births and
The actual incidences of kernicterus or severe represent a total of 42,470 readmissions for 1,532,924 live-births
hyperbilirubinemia are not available because neither is a (27.7 per 1000) reported from 1988 to 1998.16 A disparity exists
reportable condition. The incidence of severe hyperbilirubinemia between term and near-term infants in the rates for readmission
has been estimated (Table 1) from a prospective study conducted in for jaundice. In a report of all California births from 1991 to 1999,
the 1960s,11 a retrospective observational study of a population C. Phibbs (personal communication) reported that near-term
cared for in the 1990s,12 and additional prospective data from infants were consistently 6.4 to 6.6% of all well baby births (not
recent reports.13–15 Rates of readmission after the birth admitted for neonatal intensive care), but their rate of readmission
for treatment of jaundice was two- to three-fold higher than term
infants (Figure 1).
Table 1 Proposed Definitions for Severity of Hyperbilirubinemia and
Its Estimated Occurrence Research Recommendation
TSB level (mg/dl)* Percentile at Proposed Estimated Obtain data on prevalence, incidence, and mortality of severe
>72 hours agew definitions occurrencez hyperbilirubinemia and associated neurologic injury, including
kernicterus.
Z17.0 (291 mmol/L) >95th Significant B1:10
Z20.0 (342 mmol/L) >99th Severe B1:70
Z25.0 (427 mmol/L) >99.9th Extreme B1:700
Z30.0 (513 mmol/L) >99.99th Hazardous B1:10,000
B. WHAT IS THE RELATIONSHIP BETWEEN SEVERE
*TSB ¼ total serum bilirubin. HYPERBILIRUBINEMIA AND KERNICTERUS?
w
Percentiles are approximate. Available Evidence
z
Occurrence is estimated in screened and treated infants based on data reported in
Bhutani et al.,13 Stevenson et al.,14 Martinez et al.15 and Khurana et al.16 precise data
A spectrum of neuronal injury associated with hyperbilirubinemia
cannot be compiled because of differences in methodologies, patient selection, and is known as bilirubin-induced neurologic dysfunction (BIND). The
thresholds for intervention). spectrum ranges from subtle or suspicious extrapyramidal or other

Table 2 Reported Rates of Readmission for Babies Discharged as Healthy 1988 to 1998
Study (reference) State Observation Study population Total live- Total Incidence per
years births readmitted 1000 live-births

Edmonson et al. JAMA 1997;278:299. WI 1991 to 94 Statewide, nested 120,290 210 1.7
Danielsen et al. CA 1992 Statewide, linked to birth 313,748 8656 27.6
records
Pediatrics 2000;106:31. CA 1994 Statewide 301,721 7745 25.7
CA 1995 Statewide 287,371 8677 30.2
Geiger et al. Paediatr Perinat Epidemiol CA 1992 to 1994 Case control for Jaundice 68,793 156 2.0
2001;15:352.
Behram et al. South Med J 1998;91:541 VA 1994 to 1995 Community-based 2,563 74 29
Soskolne et al. Arch Pediatr Adolesc MI 1992 Private urban, 4,496 117 26
Med;150:373. community
Kotagal et al. JAMA 1999;282:1150. OH 1991 Medicaid patients 102,678 1951 21
OH 1995 17
Grupp-Phelan et al. Arch Pediatr Adolesc WA 1991 to 1995 Statewide 348,495 7388 21
Med 1999;153:1283
Liu et al. JAMA 1997;278:293 WA 1991 to 1994 Statewide, linked to birth 310,578 6444 20
records
Radmacher et al. J Ky Med Assoc 2001;99:147 KY 1994 to 1998 Hospital-based 21,628 414 19
Maisels et al. Pediatrics 1997;100:72 MI 1988 to 1994 Private, suburban 29,934 247 8
community
Brown et al. J Perinat Med 1999;27:263. NY 1995 Metropolitan city 30, 884 391 12.7

Composite data for all reports 1988 to 1998 1,532,924 42,470 27.7

Journal of Perinatology 2004; 24:650–662 651

 Bhutani et al.
35
Rates of readmission per 1000 Babies
30
25
20
15
10
0
1991
Figure 1. Rate of readmission for well babies for jaundice treatment in California (1991 to 1998) (California birth certificates were linked to the
discharge abstracts for the birth hospitalization and readmission to identify the term and near-term well baby deliveries, and to separate readmissions
for treatment of jaundice from those due to other causes.); data are presented for all well babies (E) and separated as term (K) and near-term
infants (m).
manifestations to acute encephalopathy and chronic posticteric
sequelae, although some of the signs are controversial.
Acute brain injury induced by bilirubin is associated with one or
more posticteric sequelae in survivors. These are: (1) a movement
disorder consisting of athetosis, dystonia, choreoathetosis, but also
including spasticity and hypotonia, (2) auditory dysfunction
consisting of deafness or hearing loss and auditory neuropathy
or dys-synchrony, (3) oculomotor impairments, especially of
upward gaze, and (4) dental enamel hypoplasia of the
deciduous teeth.4,17
Even though TSB is an important risk factor, bilirubin-induced
brain injury and kernicterus cannot be defined on the basis of TSB
alone. Factors including the albumin binding of bilirubin,
hemolysis, gestational age, and genetic vulnerability modify the
risk of kernicterus in an individual infant.5,18 However, there is a
paucity of studies that evaluate the impact of these risk factors on
the incidence of BIND or the occurrence of subtle sequelae or
transient neurologic abnormalities.
Contemporary prospective population-based studies that describe
the natural history of hyperbilirubinemia are unavailable; data are
limited to studies before the advent of phototherapy. In addition, no
prospective studies relate the incidence of kernicterus associated
with specific TSB values.19 Thus, characterizing the risk of brain
injury at specific levels of TSB is problematic. Furthermore, the safe
level of TSB, below which BIND does not occur in otherwise
healthy jaundiced infants, is not known. A standard definition of
kernicterus in term and near-term infants is needed for purposes of
research. This could include a threshold value for TSB, for
example, Z20 mg/dl, plus abnormalities of muscle tone on
neurological examination, auditory neurophysiological testing, and
magnetic resonance imaging.
652
Epidemiologic and Systems-Based Perspectives on Kernicterus
1992 1993 1994 1995 1996 1997 1998 1999
Calendar Year
Research Recommendations
1. Standardize definitions of severe hyperbilirubinemia, BIND,
acute bilirubin encephalopathy, kernicterus. Uniform terminol-
ogy is needed to compare databases and examine outcomes.
2. Determine the prevalence and incidence of severe hyperbilir-
ubinemia and kernicterus to estimate the risk of kernicterus at
specific levels of TSB for term and near-term infants.
3. Determine whether making a specific TSB level a reportable
condition will accomplish this purpose.
4. Develop a case–control study of adequate size to delineate the
role of bilirubin and other factors in the development of
kernicterus.
5. Define population-based standards to help predict severe
hyperbilirubinemia or, as important, the absence of risk based
on predefined peak TSB levels.
C. WHAT ARE THE CHARACTERISTICS AND THE ROOT
CAUSES OF RECENT CASES OF KERNICTERUS?
Preliminary Data
Preliminary data were presented on 125 of the 142 cases in the
United States (including uniformed services) from the Pilot
Kernicterus Registry (1992 to October 1, 2002). These infants were
discharged as healthy and were included for analysis if they
exhibited clinical signs of acute bilirubin encephalopathy and/or
posticteric sequelae, regardless of TSB level and comorbidities
(Appendix). Most cases (about 50%) were voluntarily reported by
parents or anonymously by physicians or nurses. One limitation of
the registry is that these cases of kernicterus likely represent only a
portion of affected children. Another limitation is that the
population of newborns at risk because of severe
Journal of Perinatology 2004; 24:650–662
Epidemiologic and Systems-Based Perspectives on Kernicterus
hyperbilirubinemia is unknown, so that estimates of incidence and
prevalence are unreliable. On the other hand, consistent
observations from the registry provide the basis of
recommendations for safe practices in order to prevent severe
hyperbilirubinemia and kernicterus.
Characteristics of the population reported to the Pilot
Kernicterus Registry (and individually listed in Appendix) included
84 male and 38 female cases, a racial distribution of White
(58.4%), Black (26.4%), Hispanic (8.8%), Asian (6.4%) and the
mean birth weight of 3281 g (range: 2015 to 4730). The mean
gestational age was 38 weeks (range: 35 to 42.5). The etiology of
hyperbilirubinemia in these infants, as evaluated upon readmission
that was usually before 10 days of age, is listed in Table 3. All
showed an excessive estimated rate of TSB rise (>0.20 mg/dl/hour)
from birth to readmission. Analysis of these cases suggests the
following root causes:4,5 (a) loss or lack of concern by clinicians
regarding the neurotoxic potential of bilirubin, (b) limitations on
visual recognition of jaundice as an index to initiate further
evaluation or estimate severity, (c) failure to recognize the severity
of hyperbilirubinemia at a specific age in hours; (d) failure to
ensure appropriate follow-up 1 to 2 days after early discharge (24
to 72 hours of age); (e) delay in intensive or timely interventions
before discharge or at readmission. More extensive analysis is
needed of cases of kernicterus and predefined levels of severe
hyperbilirubinemia (‘‘close calls’’) in order to better assess the
performance of health-care providers and help address Institute of
Medicine concerns, including patient (and family) centered care,
quality of care, and patient safety.
Table 3 Contributory Causes for Severe Hyperbilirubinemia and
Kernicterus Determined at Subsequent Readmission (Preliminary
Data Voluntarily Reported to the Pilot Kernicterus Registry)
Major contributory Postnatal age at readmission (n ¼ 116)
cause of
Hyperbilirubinemia
r3 days 4 to 7 days
N¼8 N ¼ 85
Hemolysis 0% 20%
G6PD deficiency 25% 24.7%
Idiopathic 50% 31.8%
Birth trauma 0% 17.6%
Other 25% 5.9%
Hemolysis was due to ABO or minor blood group incompatibility, extensive bruising,
cephalhematoma, hereditary spherocytosis, etc. Other causes include birth trauma,
sepsis, galactosemia, Crigler-Najjar syndrome. Idiopathic group represents those infants
in whom no contributory cause could be ascertained following comprehensive clinical
evaluation and follow-up. Several infants had additional or multiple factors such as
dehydration and/or excessive weight loss that would have contributed to the excessive
bilirubin load.
Journal of Perinatology 2004; 24:650–662
Bhutani et al.
Research Recommendations
1. Conduct a comprehensive analysis of Registry cases to identify
common characteristics, delineate the lapses in care that may
have contributed to the occurrence of kernicterus, and
determine the sentinel events that may have predicted the
occurrence of kernicterus.
2. Test the hypothesis that severe hyperbilirubinemia or
kernicterus that affects babies discharged as healthy can be
predicted before discharge.
3. Assess the feasibility of a national reporting system and database
for cases of pre-defined severe hyperbilirubinemia and
kernicterus.
4. Assess the feasibility of developing a systematic centralized
review process, including root cause analysis, for prospective
reported cases of severe hyperbilirubinemia that can be
subsequently used to develop targeted education and systems
improvements.
5. Develop measurement tools to assess whether a centralized
review process and interventions improve outcome.
D. WHAT SHOULD THE TARGET INDICATOR BE FOR
PUBLIC HEALTH SURVEILLANCE OF KERNICTERUS AND/
OR HYPERBILIRUBINEMIA?
At present, severe hyperbilirubinemia remains the most plausible
surrogate indicator for kernicterus even though the risk of
kernicterus at specific TSB ranges is estimated by clinical
consensus rather than evidence-based criteria (Table 4).
Surveillance for severe hyperbilirubinemia has distinct
advantages. It describes an at-risk population, similar to identifying
a population with hypertension regardless of its cause or its clinical
outcome. TSB results are immediately available and objective, and
can be reported rapidly. The inclusion of all cases, rather than just
those with sequelae, would allow study of the risk of kernicterus in
a population with hyperbilirubinemia, as well as study of the
frequency and effects of any intervention. The TSB level at which
>7 days cases might become reportable can be adjusted up or down based
N ¼ 23 on risk and benefits. The immediacy and greater frequency of this
outcome also make it potentially more useful for quality
20.7% improvement efforts. Any initiative to begin surveillance for severe
12.5%
hyperbilirubinemia should be accompanied by efforts to improve
50.0%
standardization and minimize inter-laboratory variability.20
12.5%
8.3%
In general, there are at least four possible targets for public
health surveillance related to kernicterus (Table 5). The first
consideration is kernicterus itself. This disorder is the focus of
current concern. However, the diagnosis may be delayed or under-
reported. In addition, occurrences of kernicterus may be too
infrequent (and too late) to provide feedback to health-care systems
and providers that might reduce the risk of future cases.
Surveillance for kernicterus would not capture other adverse effects
653
 Bhutani et al. Epidemiologic and Systems-Based Perspectives on Kernicterus

Recommendations
Table 4 Readmission TSB Levels in 118 of the 125 Cases of Infants
with Kernicterus Discharged as Healthy from Newborn Nurseries 1. Identify an appropriate target indicator(s) for surveillance based
(Preliminary Report from the Pilot Kernicterus Registry) These are upon advantages and disadvantages (Table 5).
listed along with current opinions regarding the potential risk of
kernicterus in untreated infants with severe hyperbilirubinemia
TSB levels (mg/dl) Number of cases Opinions of risk in untreated
E. HAVE SYSTEMS-BASED APPROACHES FOR THE MAN-
reported with infants AGEMENT OF NEWBORN JAUNDICE BEEN VALIDATED?
kernicterus* Available Evidence
(n ¼ 116) Because of the concern for the reemergence of kernicterus,2–4 AAP5
and JCAHO8 recommend a universal systematic approach to the
< 20.0 0 Risk unlikely and unproven. management of newborn jaundice, with the aim of reducing the
Possible risk of subtle effects. incidence of severe hyperbilirubinemia8,9,21–23 and kernicterus.
Relationship of actual TSB level
This involves using clinical risk factors analysis and/or
with onset of injury is often unclear
measurement of predischarge TSB levels plotted an hour-specific
20.0 to 24.9 11 Risk unlikely but unproven (infants
nomogram to target appropriate follow-up and intervention. No
with other factors may be
vulnerable). Cases have been
prospective studies have compared or confirmed the effectiveness of
reported of kernicterus associated such approaches. Whether a public health campaign to increase
with these levels parental and provider awareness of jaundice and its potential
25.0 to 29.9 15 High level of concern although consequences would reduce adverse outcomes is also unknown.
actual risk is unknown. Some
infants may not manifest acute Research Recommendations
neurological injury 1. Evaluate the recommendations for systems-based approaches
Z30.0 90 Risk is increasingly likely although for the prevention and management of severe hyperbilirubine-
actual risk is unknown. Some mia. Approaches based on risk factors for severe hyperbilir-
infants may be protected from ubinemia or predischarge hour-specific TSB measurements
neurologic injury with expeditious should be prospectively validated for safety, costeffectiveness,
and efficient interventions
and applicability to ethnically and racially diverse populations.
*Based on peak measured TSB values (these measured values may not reflect the peak 2. Assess whether systematic prediction of severe neonatal
hyperbilirubinemia levels experienced by infants because of lack of serial
hyperbilirubinemia prevents kernicterus in a cost-effective,
measurements or potential lowering of TSB levels concurrent to onset of acute
bilirubin injury). practical and safe manner.
3. Evaluate the epidemiologic impact of a public health campaign
to reduce adverse outcomes of severe neonatal hyperbilirubi-
nemia.
of hyperbilirubinemia, including less typical sequelae and
complications of exchange transfusion.
Like kernicterus, cerebral palsy is a highly relevant and F. ARE THERE BIOLOGICAL OR GENETIC MARKERS THAT
clinically significant indicator. The diagnosis of cerebral palsy is CAN BE USED TO BETTER DEFINE INFANTS AT RISK FOR
already a matter of public health concern. Surveillance for cerebral SEVERE HYPERBILIRUBINEMIA?
palsy would allow studies of risk in children with different TSB Insufficient Evidence
levels, including those in whom TSB was never measured. However, The genetic contribution to neonatal hyperbilirubinemia due to
the proportion of cerebral palsy due to kernicterus is not known, disorders of hepatic bilirubin conjugation and to the pathogenesis
surveillance for cerebral palsy may be insensitive to changes in of neuronal cell injury caused by hyperbilirubinemia needs further
kernicterus incidence, and feedback to providers would be investigation.24,25 For example, early jaundice is greater in
nonspecific and delayed. newborns homozygous for the polymorphism associated with
Yet another surveillance strategy could be to monitor rates of Gilbert syndrome compared to those with the normal sequence or
readmission for treatment of hyperbilirubinemia or use of home heterozygous for the mutation.26 The incidence of
phototherapy. Concomitant with incidence of severe hyperbilirubinemia is also increased in infants who have the
hyperbilirubinemia, these offer useful indices of occurrence and Gilbert polymorphism and glucose-6-phosphatase dehydrogenase
outcome. On the other hand, interpretation is limited because (G6PD) deficiency.24 An investigation of microarray gene
intervention thresholds for severe hyperbilirubinemia have not been expression of hereditary disorders of unconjugated
yet standardized. hyperbilirubinemia such as Gilbert, Arias, and Crigler-Najjar

654 Journal of Perinatology 2004; 24:650–662

Epidemiologic and Systems-Based Perspectives on Kernicterus Bhutani et al.

Table 5 Potential Targets for Surveillance of BIND

Indicator or Clinical relevance Age at identification Potential limitations when used as a surveillance target
surrogate

Kernicterus Index disease Usually during infancy and Clinical criteria not yet standardized
childhood
Often under-reported
Often undiagnosed
Other manifestations of BIND missed
Long interval between change in neonatal practices to outcome
Medicolegal concerns may delay or inhibit identification

Cerebral palsy Includes cases of Usually during infancy Dependent on identification of athetoid/dystonic features
(existing national Kernicterus
public health issue)
Other manifestations of BIND not identified
Causality hindered if there are no neonatal measures of hyperbilirubinemia
Concerns of long interval between change in neonatal practices to outcome

Readmission for At-risk population During neonatal age Requires standardized guidelines for severe hyperbilirubinemia
jaundice treatment
(existing public
health issue)
Requires standardized guidelines and implementation for interventions
Requires linkage to birth records
Requires compliance by clinicians and families

Severe At-risk population During neonatal age Requires bilirubin measurement and follow-up for all infants
hyperbilirubinemia
Requires accurate, standardized and centralized reporting by laboratories
Allows for objective and non biased reporting from laboratories
Requires follow-up of high-risk infants for signs of BIND

syndromes may elucidate possible coinheritance with G6PD
deficiency, beta-thalassemia, and hereditary spherocytosis and
identify infants at increased risk of severe hyperbilirubinemia.27–29
At this stage, it is too early to know whether genetic epidemiology
of hyperbilirubinemia would contribute to the prevention of BIND.
Research Recommendation
Explore the feasibility of using diagnostic oligonucleotide
microarrays for the known mutations of target genes to identify
infants at increased risk of severe hyperbilirubinemia or those who
have sustained kernicterus.
CONCLUSION
Infants discharged as healthy from their birth hospitals should
have a safe transition to home, avoiding morbidity due to jaundice
and other disorders. Prevention of readmission for severe
hyperbilirubinemia in otherwise healthy infants, acute bilirubin
encephalopathy, and chronic posticteric sequelae is a matter of
public health and societal concern. Accurate data on the incidence
of severe neonatal hyperbilirubinemia and associated adverse
outcomes are fundamental to the planning, implementation, and
assessment of interventions, including public policy and
educational programs, to prevent adverse outcomes.
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19. Ip S, Glicken S, Kulig J, O’Brien R, Sege R. Management of Neonatal
Hyperbilirubinemia. Summary, Evidence Report/Technology Assessment.
Number 65. AHRQ Publication No. 03 E005, March 2002. Agency for
Healthcare Research and Quality, Rockville, MD.
20. Vreman HJ, Verter J, Stevenson DK. Interlaboratory variability of bilirubin
measurements. Clin Chem. 1996;42:869–73.
21. Sheridan SE. Kernicterus parents’ group. J Pediatr 2002;141:597.
22. Bhutani VK, Johnson LH. Newborn jaundice and kernicterus – health and
societal perspectives. Indian J Pediatr 2003;70:407–16.
23. Bhutani VK, Johnson LH, Keren R. Diagnosis and management of
hyperbilirubinemia in the term neonate: for a safer first week. Pediatr Clin
North Am. (in press).
24. Watchko JF, Daood MJ, Biniwale M. Understanding neonatal hyperbilir-
ubinemia in the era of genomics. Semin Neonatol 2002;7:143–52.
25. Dennery PA, Seidman DS, Stevenson DK. Neonatal hyperbilirubinemia. N
Engl J Med 2001;344:581–90.
26. Bancroft JD, Kreamer B, Gourley GR. Gilbert syndrome accelerates
development of neonatal jaundice. J Pediatr 1998;132:656–60.
27. Beutler E, Gelbart T, Demina A. Racial variability in the UDP-
glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism
for regulation of bilirubin metabolism? Proc Natl Acad Sci USA
1998;95:8170–4.
28. Bosma PJ, Chowdhury JR, Bakker C, et al. The genetic basis of the reduced
expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert’s
syndrome. N Engl J Med 1995;333:1171–5.
29. Kaplan M, Renbaum P, Levy-Lahad E, Hammerman C, Lahad A, Beutler E.
Gilbert syndrome and glucose-6-phosphate dehydrogenase deficiency: a
dose-dependent genetic interaction crucial to neonatal hyperbilirubinemia.
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APPENDIX A Table A1 summarizes the data from Pilot
Kernicterus Registry.
Journal of Perinatology 2004; 24:650–662
Journal of Perinatology 2004; 24:650–662

Epidemiologic and Systems-Based Perspectives on Kernicterus

Table A1 Clinical Characteristics of 125 from 142 Infants with Kernicterus Discharged as Healthy (Pilot Kernicterus Registry)
Source/ Birth BW GA Sex/race Discharge Readmit Readmit Peak Acute Ex Tx Photo Likely cause Follow- Icteric Comments
code year (g) (weeks) day age TSB TSB BIND Rx up sequelae
(day)

C-001 1994 3260 36 m/W 0.5 4.0 35.0 35.0 Advanced Yes Yes Idiopathic Yes Moderate ABO Coombs neg
C-002 1993 3725 39 m/A 0.5 4.0 40.2 40.2 Advanced Yes Yes Hemolysis Yes Severe ABO Coombs pos
L-003 1988 3785 39 unk/H 0.5 4.0 45.0 45.0 Advanced Yes Yes Idiopathic Yes Severe ExTx delayed 12 hours.
(Jehovah Witness)
M-004 1996 3000 36 f/B 0.5 4.5 40.9 40.9 Advanced Yes Yes Idiopathic Yes Severe Hct 45%, wt loss
M-005 1997 3884 38 m/W 0.5 5.0 46.0 46.0 Advanced Yes Yes Hemolysis Yes Severe ABO Coombs neg, jaundice
<24 hours age, Na 149 mEq/L
M-006 1993 3856 41 f/W 1.0 2.5 22.4 22.4 Advanced No Yes Idiopathic Yes Severe Dehydration, Na 153 mEq/l
L-007 1995 3544 39 f/A 1.0 3.0 27.8 27.8 Subtle Yes Yes Infection Yes None Urosepsis (E. coli), MRI (at day
5): inc. globus pallidus signal
M-008 1995 2920 37 m/B 1.0 3.0 33.0 36.7 Advanced No Yes G6PD Yes Severe Hct 40%, Presumed sepsis
C/M-009 1990 2015 36 f/W 1.0 3.5 41.8 41.8 Advanced Yes Yes Idiopathic Yes Severe Plethora, ABO Coombs neg
M-010 1998 3629 39 f/W 1.0 3.5 52.0 52.0 Advanced Yes Yes Idiopathic Yes Severe Family history, jaundice <24
hours age
L/C-011 1995 2614 39 f/B 1.0 4.0 33.0 33.0 Moderate No Yes Idiopathic Yes Moderate Hct 43%
P-012 1999 4026 39 m/W 1.0 4.0 39.0 45.0 Advanced Yes Yes Birth trauma Yes Severe Precipitous labor, family
history of jaundice
P-013 2002 3714 40 m/W 1.0 4.0 44.8 44.8 Advanced Yes Yes Hemolysis Yes Severe Congenital spherocytosis, Hct
27%, peak TSB 49 mg/dl
P-014 2000 4200 35 f/W 1.0 5.0 27.0 31.5 Subtle No Yes Birth trauma Yes Severe Plethora at birth
L/C-015 1994 3489 39 m/W 1.0 5.0 30.6 30.6 Advanced Yes Yes Idiopathic Yes None Hct 38%, Albumin before ExTx
L-016 1996 2637 39 m/H 1.0 5.0 34.8 34.8 Moderate Yes Yes Idiopathic Yes None Hct 48%
M-017 1996 3450 39 f/H 1.0 5.0 37.0 46.0 Advanced Yes Yes Hemolysis Yes Severe ABO Coombs pos, jaundice
<24 hours age
L-018 1993 3147 39 m/B 1.0 5.0 42.5 42.5 Advanced Yes Yes G6PD Yes Severe Mild anemia, no evident
hemolysis
M-019 1992 3685 39 m/B 1.0 5.5 46.8 46.8 Advanced No Yes G6PD Died Died Moribund on readmission
C-020 1995 3130 39 m/H 1.0 6.0 28.5 28.5 Advanced Yes Yes Hemolysis Yes Severe ABO, Coombs unk, Hct 42%
M-021 1997 3680 37 m/W 1.0 6.0 29.3 32.5 Advanced Yes Yes Birth trauma Yes Severe 13% wt loss at day 6, Hct 44%
M-022 1994 3048 35 f/W 1.0 6.0 31.0 31.0 Advanced No Yes Birth trauma Yes Severe 11% wt loss at day 6

Bhutani et al.
P-023 2002 2745 38 f/W 1.0 6.0 46.2 46.2 Advanced Yes Yes Hemolysis No Severe ABO Coombs pos, jaundice
<24 hours age
P-024 1993 3487 37 m/H 1.0 8.5 41.3 53.9 Advanced Yes Yes Birth trauma Yes Severe Hct 43%
P-025 1994 3090 37 m/W 1.0 12.0 41.0 41.0 Advanced Yes Yes Idiopathic Yes Severe ABO Coombs neg 17% wt loss
(day 12)
657
658

Table A1 (Continued)
Source/ Birth BW GA Sex/race Discharge Readmit Readmit Peak Acute Ex Tx Photo Likely cause Follow- Icteric Comments

Bhutani et al.
code year (g) (weeks) day age TSB TSB BIND Rx up sequelae
(day)
P-026 1997 3433 39 m/W 1.0 None None None Moderate No No Idiopathic Yes Moderate ABO, Coombs: unk, prolonged
jaundice (>8 weeks)
M-027 1993 3355 37 f/W 1.0 None Not None Advanced No No Hemolysis Yes Severe ABO Coombs: unk,16% wt. loss
done d15, arching (at age 1 week),
Peak TSB unk
C-028 1999 3720 40.5 m/B 1.5 3.0 21.4 21.4 Moderate No Yes Idiopathic Lost UNK Lost to follow-up
C-029 1991 2865 39 m/H 1.5 3.0 38.4 38.4 Advanced Yes Yes G6PD No Severe Hct 40%, abnormal RBC smear
M-030 1991 3374 39 f/W 1.5 3.0 38.4 44.5 Advanced Yes Yes Idiopathic Yes Severe Hct 52%, father with Gilbert’s
syndrome
C-031 1998 3600 37 f/W 1.5 3.5 38.5 38.5 Subtle Yes Yes Idiopathic <1 yr Moderate ABO Coombs neg, Hct 64%
C-032 2001 3994 38 m/W 1.5 4.0 22.0 27.0 Moderate Yes Yes Idiopathic Yes None 14% wt loss at day 4, Na
152 mEq/l
M-033 1999 3510 39 m/B 1.5 4.0 33.6 37.2 Moderate No Yes Hemolysis Yes Severe ABO Coombs neg, Hct 41%
P-034 2001 3468 38.5 m/W 1.5 4.0 38.0 41.0 Advanced Yes Yes Birth trauma Yes Severe Jaundice noted at age 24 hours
L-035 2000 3203 38 f/H 1.5 3.0 46.9 46.9 Advanced Yes Yes Idiopathic Yes None Sibling treated for jaundice
P-036 2001 3572 39.6 m/W 1.5 4.5 28.3 28.3 Subtle No Yes Birth trauma Yes Severe Family (sibling) history of
jaundice
M/L-037 1991 2665 36 f/B 1.5 4.5 37.0 39.5 Advanced Yes Yes G6PD Yes Severe Hemolysis trigger unk, Hct 28%
M-038 1996 2892 36 f/W 1.5 5.0 27.0 28.7 Moderate No Yes Birth trauma Yes Severe Partially treated perinatal
sepsis, Hct 50%, Na 150 mEq/l
M-039 1997 3985 39 f/A 1.5 5.0 30.4 37.8 Advanced YES Yes Birth trauma Yes Moderate ABO Coombs neg,15% wt loss at
day 5, Na 152 mEq/l

Epidemiologic and Systems-Based Perspectives on Kernicterus

C-040 1996 2500 38 m/B 1.5 5.0 41.3 41.3 Advanced Yes Yes G6PD Died Severe Urosepsis, Hct 22%, died at 6
months
M-041 1993 2925 38 m/B 1.5 5.0 45.9 45.9 Advanced Yes Yes G6PD Died Died Incomplete evaluation of
hyperbilirubinemia
Journal of Perinatology 2004; 24:650–662

L-042 1994 2840 37 m/A 1.5 5.0 49.2 49.2 Advanced Yes Yes G6PD Died Died 13.6% wt loss at day 5,
neutropenia, no hemolysis
M-043 2000 3180 39 m/W 1.5 5.0 59.9 59.9 Moderate Yes Yes Hemolysis Yes Severe ABO, Coombs pos, jaundice at
age 9 hours, wt loss >20%
M-044 1992 2380 36 f/A 1.5 5.5 32.0 32.0 Advanced Yes Yes Birth trauma Yes Severe 13% wt loss at day 5.5,
Plethora, Hct 64%
M-045 1995 2863 37 m/W 1.5 5.5 34.6 34.6 Advanced No Yes Hemolysis Yes Severe ABO Coombs: unk, otitis media
C-046 1997 3650 38 m/A 1.5 6.0 25.6 25.6 Advanced Yes Yes G6PD Yes None Albumin before exchange, Hct
50%, Na 154 mEq/l
M-047 2001 3310 36 m/H 1.5 6.0 33.5 33.5 Subtle Yes Yes Idiopathic Yes Severe Bruising, Hct 42%
Journal of Perinatology 2004; 24:650–662

Epidemiologic and Systems-Based Perspectives on Kernicterus

Table A1 (Continued)
Source/ Birth BW GA Sex/race Discharge Readmit Readmit Peak Acute Ex Tx Photo Likely cause Follow- Icteric Comments
code year (g) (weeks) day age TSB TSB BIND Rx up sequelae
(day)

L-048 1995 3400 41 m/B 1.5 6.0 41.0 41.0 Advanced Yes Yes G6PD Yes Severe Concurrent sepsis (E. coli)
C-049 1996 4280 39 m/A 1.5 6.0 45.7 45.7 Advanced Yes Yes G6PD Yes Moderate Hemolysis trigger: mothball
exposure
L-050 1988 unk 39 unk/B 1.5 7.0 24.0 28.0 Advanced Yes Yes G6PD Yes Severe Direct bilirubin 9 mg/dl at day
7
P-051 2002 3057 38.5 m/W 1.5 7 31.0 41.0 Subtle No Yes Hemolysis Yes Moderate Wt loss: 15%, ABO, Coombs pos
P-052 2000 3317 36 m/W 1.5 7.0 35.0 35.0 Advanced Yes Yes Hemolysis Yes None Plethora, 17% wt loss at day 7.0
C-053 1994 4455 41 m/W 1.5 7.0 42.0 42.0 Advanced Yes Yes Idiopathic Lost Severe Follow-up incomplete
M-054 1990 2608 36 m/B 1.5 8.0 33.7 36.4 Advanced Yes Yes Idiopathic Yes Severe Hct 43%
P-055 1989 4224 38 m/W 1.5 8.5 37.0 39.0 Moderate Yes Yes Idiopathic Yes Severe Seen by MD at day 7.5, no TSB
done
M-056 1995 2700 36 m/B 1.5 10.0 32.5 32.5 Advanced Yes Yes Idiopathic Yes Severe Hct 41%
C-057 1996 3150 36 m/W 1.5 11.0 40.0 40.0 Advanced Yes Yes Hemolysis Yes Severe Hct 22%, abnormal RBC
morphology, hemolysis cause
unk.
P-058 1997 3033 36.5 m/W 1.5 13.0 25.0 27.7 Advanced No Yes Hemolysis Yes Severe Hct 18%, abnormal RBC
morphology
M-059 2002 3199 37 m/W 1.5 19.0 44.7 44.7 Advanced Yes Yes Idiopathic Yes Severe Hct 43%, direct bilirubin
1.7 mg/dl
M-060 1994 3062 37 m/W 1.5 None 31.6 31.6 Moderate No Yes Hemolysis Yes Severe ABO Coombs pos, home
phototherapy day 4 for TSB
31.6 mg/dl
P-061 2000 2951 38 f/W 1.5 None Not None Subtle No No Birth trauma Yes Severe First office visit at d12
done (TSB ¼ 13 mg/dl), peak TSB
Unk.
M-062 2001 2715 37.5 f/B 2.0 3.5 35.0 38.4 Advanced Yes Yes Hemolysis Yes Severe ABO Coombs pos, Hct 31%, retic
18%, Bacteremia g+cocci
bacillus species
M-063 2000 2438 36 f/W 2.0 3.5 35.4 35.4 Advanced No Yes Idiopathic Died Died Plethora, bruising
M-064 1999 3626 38 m/B 2.0 3.5 39.0 44.0 Moderate Yes Yes G6PD No Severe 9% wt loss at day 3.5, Hct 50%
M-065 2001 3260 36 m/B 2.0 4.0 33.0 34.0 Subtle Yes Yes Idiopathic Yes Severe ABO Coombs negative, IDM

Bhutani et al.
M-066 1984 2850 36.5 m/W 2.0 4.0 33.9 39.8 Advanced Yes Yes Birth trauma Yes Moderate Hct 53%, family (sibling)
history of jaundice
M-067 1992 2825 37.5 m/B 2.0 4.0 34.5 34.5 Advanced No Yes Idiopathic Yes Severe Hct 45%
C-068 1995 3459 39 m/B 2.0 4.0 39.2 39.2 Advanced Yes Yes G6PD Yes Severe Neutropenia, presumed sepsis,
659

Hct 38%
660

Table A1 (Continued)
Source/ Birth BW GA Sex/race Discharge Readmit Readmit Peak Acute Ex Tx Photo Likely cause Follow- Icteric Comments

Bhutani et al.
code year (g) (weeks) day age TSB TSB BIND Rx up sequelae
(day)
M-069 1993 2625 40 M/B 2.0 4.0 44.2 46.0 Advanced Yes Yes G6PD Yes Severe Hct 45%, hemolytic trigger:
mothball exposure
L-070 1992 3400 39 m/H 2.0 4.0 50.1 50.1 Advanced Yes Yes G6PD Yes Severe Sepsis (E. coli)
C/L-071 2002 2609 40 m/B 2.0 4.5 31.7 31.7 Advanced No Yes G6PD Died Died 9% wt loss at day 4.0, Hct 34%
P-072 2002 3402 38 m/W 2.0 4.5 38.0 38.0 Advanced Yes Yes Idiopathic Yes Severe Jaundice noted before 24 hours
age
L-073 1989 3150 39 m/W 2.0 5.0 28.7 29.5 Subtle Yes Yes Hemolysis Yes None ABO Coombs pos, failed BAER
at d/c (passed at 6 months)
P-074 2001 2384 35 M/W 2.0 5.0 31.0 31.0 Moderate Yes Yes Idiopathic Yes Severe Mom has congenital
spherocytosis
M-075 1990 2790 36.5 m/W 2.0 5.0 36.8 39.8 Advanced Yes Yes G6PD Yes Severe E. coli sepsis, birth trauma,
ABO Coombs neg
M-076 1995 4687 39 f/H 2.0 5.0 37.0 46.5 Advanced Yes Yes Hemolysis Yes Severe ABO Coombs neg, abnormal
RBC morphology, Hct 39
M-077 1991 2835 36 f/W 2.0 5.0 41.1 44.4 Advanced Yes Yes Hemolysis Yes Severe 20% wt loss at day 5
M-078 1993 3260 39 f/H 2.0 6.0 30.2 38.0 Advanced Yes Yes Hemolysis Yes Severe Plethora, hemolysis cause: unk
M-079 1996 3350 36 m/W 2.0 6.0 34.7 34.7 Advanced Yes Yes Idiopathic Yes Severe Hct 56%
P-080 2000 3178 37.5 m/W 2.0 6.0 35.0 42.0 Advanced Yes Yes Idiopathic Yes Severe 14% wt loss at day 6
C-081 1987 3175 37 m/W 2.0 6.0 41.8 41.8 Advanced Yes Yes Idiopathic Yes Severe 18% wt loss at day 6, Hct 57%
P-082 2002 3320 37 f/W 2.0 6.5 25.3 25.3 Advanced No Yes Birth trauma Yes Moderate ABO Coombs pos, Hct 51%,
jaundice <24 hours
M-083 2000 3856 37.5 m/W 2.0 6.5 28.6 36.2 Advanced Yes Yes Birth trauma Yes Severe Hct 45%

Epidemiologic and Systems-Based Perspectives on Kernicterus

M-084 1991 3310 38 m/B 2.0 7.0 21.5 36.0 Advanced Yes Yes G6PD No Severe TSB 36 at day 10.8, nosocomial
sepsis day 11
C-085 1998 unk 39 f/B 2.0 7.0 48.0 48.0 Advanced Yes Yes Infection Yes Severe Vomiting for 4 days,
intraosseous fluids. Hct 28%
Journal of Perinatology 2004; 24:650–662

P-086 2002 2724 37 m/B 2.0 7.0 33.0 33.0 Moderate Yes Yes G6PD Yes Moderate Family (maternal) history of
jaundice
P-087 1994 3572 38 m/W 2.0 7.0 39.0 39.0 Advanced Yes Yes Idiopathic Yes Mild Apneic spells on admission
P-088 1998 3263 39 f/W 2.0 7.0 42.0 42.0 Advanced Yes Yes Idiopathic Yes Severe Atraumatic forceps delivery
C-089 2002 2700 35.5 m/B 2.0 7.0 46.2 46.2 Advanced Yes Yes G6PD Yes Severe Urosepsis (Citrobacter)
L-090 1996 3210 39 m/W 2.0 7.0 47.9 47.9 Advanced Yes Yes Galactosemia Yes Severe 15% wt loss at day 7
C-091 1996 2808 39 m/B 2.0 8.0 30.0 30.0 Moderate Yes Yes G6PD Yes None Cephalohematoma
M-092 1987 2700 36.5 m/B 2.0 8.0 32.0 35.0 Advanced Yes Yes Idiopathic Yes Severe ABO Coombs neg, Hct 47%
L-093 1992 unk 39 unk/W 2.0 8.0 49.4 49.4 Advanced Yes Yes Idiopathic Yes Severe Persistent incr. signals in
globus pallidus on multiple
MRI <1 year age
Journal of Perinatology 2004; 24:650–662

Epidemiologic and Systems-Based Perspectives on Kernicterus

Table A1 (Continued)
Source/ Birth BW GA Sex/race Discharge Readmit Readmit Peak Acute Ex Tx Photo Likely cause Follow- Icteric Comments
code year (g) (weeks) day age TSB TSB BIND Rx up sequelae
(day)
M-094 1992 3050 38 f/W 2.0 10.0 49.4 49.4 Advanced Yes Yes Hemolysis Yes Severe ABO, Coombs neg, Hct 23%
C-095 1997 3415 39 m/W 2.0 11.5 21.6 21.6 Advanced No Yes Infection Yes Severe Clostridium sepsis, >20% wt
loss at day 11.5, Na 166 mEq/l,
ABO Coombs neg
M-096 1992 3175 35 m/H 2.0 14.0 29.4 32.7 Moderate Yes Yes Birth trauma Yes Severe Hct 51%
P-097 2000 3320 35.7 f/W 2.0 None not None Subtle No No Idiopathic Yes Severe Prolonged marked jaundice
done (>6weeks)
P-098 2001 4075 39 m/W 2.0 None Not Unk Moderate No No Idiopathic Yes Severe Prolonged jaundiced (>8
done weeks), TSB 20 done and
recorded at day 4.
M-099 2001 3487 39 m/B 2.5 4.0 41.4 41.4 Advanced Yes Yes G6PD Yes Severe Hct 42%, no sepsis
P/M-100 1992 3289 39 f/W 2.5 4.5 23.8 23.8 Advanced No Yes Birth trauma Yes Severe 20% wt loss at day 4.5, Hct 50%
M-101 2000 3346 36.5 m/W 2.5 5.0 39.5 39.5 Advanced Yes Yes Idiopathic Yes Severe 16% wt loss at day 5
C-102 1994 3025 36 f/W 2.5 5.5 36.0 36.0 Subtle Yes Yes Idiopathic Yes Severe 15% wt loss at day 5.5
P-103 1993 3062 37 m/A 2.5 7.0 31.4 31.4 Advanced Yes Yes G6PD Yes Severe Birth trauma, 15% wt. loss at
day 7, Na 161 mEq/l
P-104 1989 3260 38.5 m/W 2.5 7.0 40.0 40.0 Advanced Yes Yes Birth trauma Yes Severe Jaundice <24 hours age
P-105 1987 2977 40 m/W 2.5 9.0 24.5 24.5 Advanced No Yes Idiopathic Yes Severe Hct 56%, TSB at day 8.5 was
23.5 mg/dl
P-106 1998 4309 38 m/W 2.5 12.5 29.3 29.3 Moderate No Yes Hemolysis Yes Severe ABO Coombs neg, Hct 43%,
jaundice < 24 hours
C-107 1993 3296 38 m/W 2.5 15.0 28.9 28.9 Advanced No Yes Idiopathic Yes Severe Weak suck, arching (age 1
week)
P-108 1998 3757 36 m/W 3.0 5.0 30.0 30.0 Subtle No Yes Birth trauma Yes Moderate Prolonged jaundiced (>6
weeks)
L-109 1985 3771 37 m/W 3.0 5.0 39.0 39.0 Advanced Yes Yes Idiopathic Yes Severe >20% wt loss at day 5, Hct 70%
C-110 2002 unk 39 m/B 3.0 6.0 39.0 39.0 Moderate Yes Yes Infection Yes Moderate Probable urosepsis
M-111 1993 2905 36 f/B 3.0 6.0 43.0 43.0 Advanced Yes Yes Hemolysis Yes Severe Hct 36%, abnormal RBC
morphology
L-112 1979 2820 37 m/W 3.0 7.0 49.7 49.7 Advanced Yes Yes Idiopathic Yes Severe 11% wt loss at day 7, Hct 50%
P-113 1999 3348 39 f/W 3.0 10.0 24.0 24.0 Moderate No Yes Idiopathic Yes Moderate Prolonged jaundiced >4 weeks

Bhutani et al.
L-114 1989 4280 39 m/W 3.0 10.0 40.3 40.3 Advanced Yes Yes Idiopathic Yes Severe Hct 49%
P-115 1994 3632 39.5 m/W 3.0 None None None Moderate No No Idiopathic Yes Moderate Jaundice >8weeks, peak TSB
unk
M-116 1986 2977 37 f/W 3.5 16.0 20.7 20.7 Moderate No Yes Idiopathic Yes Moderate Plethora
C-117 1987 3250 39 f/W 4.0 8.0 41.0 41.0 Moderate Yes Yes Birth trauma No Moderate Hct 40%
661
 662

Table A1 (Continued)
View publication stats

Source/ Birth BW GA Sex/race Discharge Readmit Readmit Peak Acute Ex Tx Photo Likely cause Follow- Icteric Comments

Bhutani et al.
code year (g) (weeks) day age TSB TSB BIND Rx up sequelae
(day)
P-118 1994 2325 38 m/W 4.0 None None None Moderate No No Idiopathic Yes Moderate 12% wt loss at day 4
C-119 2000 2977 37 m/B 6.0 13.0 54.0 54.0 Advanced Yes Yes G6PD Yes Severe 10.5% wt loss at day 13
C-120 1999 3700 38 m/W HB 3.0 41.3 41.3 Advanced Yes Yes Crigler-Najjar Lost Severe ABO Coombs neg, abnormal
RBC morphology, Hct 66%, Na
149 mEq/l
C-121 1998 Unk Unk m/W HB 5.0 40.0 40.0 Advanced Yes Yes Crigler-Najjar Lost Severe Follow-up incomplete.
C-122 1999 4730 39 m/W HB 6.0 24.0 24.0 Advanced Yes Yes Infection Yes Severe Home birth Shoulder dystocia;
sepsis (E. coli), renal abscess.
L-123 1990 4026 37 f/W HB 7.0 44.7 44.7 Advanced Yes Yes Idiopathic Yes Severe 20% wt loss at day 7, Hct 54%
C-124 2002 3632 42.5 f/W HB 27.0 28.1 28.1 Moderate No Yes Hemolysis No Severe Cong Spherocytosis, Hct 27%
C-125 1992 2500 36.5 f/B None 8.0 42.0 46.0 Advanced Yes Yes G6PD Yes Severe Family history of jaundice, 2
sibs had ExTx
C: colleague; f: female; HB: home birth; Hct: hematocrit; L: literature; m: male; M: malpractice case; neg: negative; P: parent; pos: positive; retic: reticulocyte count; Unk: Unknown.

Epidemiologic and Systems-Based Perspectives on Kernicterus

Journal of Perinatology 2004; 24:650–662