DOI: 10.1542/peds.

2004-0899
2004;114;917 Pediatrics
Gautham K. Suresh and Robin E. Clark
Newborn Infants
Cost-Effectiveness of Strategies That Are Intended to Prevent Kernicterus in

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Cost-Effectiveness of Strategies That Are Intended to
Prevent Kernicterus in Newborn Infants
Gautham K. Suresh, MD, DM, MS*, and Robin E. Clark, PhD
ABSTRACT. Objective. There is concern about an in-
creasing incidence of kernicterus in healthy term neo-
nates in the United States. Although the incidence of
kernicterus is unknown, several potential strategies that
are intended to prevent kernicterus have been proposed
by experts. It is necessary to assess the costs, benefits,
and risks of such strategies before widespread policy
changes are made. The objective of this study was to
determine the direct costs to prevent a case of kernicterus
with the following 3 strategies: (1) universal follow-up in
the office or at home within 1 to 2 days of early newborn
discharge, (2) routine predischarge serum bilirubin with
selective follow-up and laboratory testing, and (3) rou-
tine predischarge transcutaneous bilirubin with selective
follow-up and laboratory testing.
Methods. We performed an incremental cost-effec-
tiveness analysis of the 3 strategies compared with cur-
rent practice. We used a decision analytic model and a
spreadsheet to estimate the direct costs and outcomes,
including the savings resulting from prevented ker-
nicterus, for an annual cohort of 2 800 000 healthy term
newborns who are eligible for early discharge. We used
a modified societal perspective and 2002 US dollars. With
each strategy, the test and treatment thresholds for hy-
perbilirubinemia are lowered compared with current
practice.
Results. With the base-case assumptions (current in-
cidence of kernicterus 1:100 000 and a relative risk re-
duction [RRR] of 0.7 with each strategy), the cost to
prevent 1 case of kernicterus was $10 321 463, $5 743 905,
and $9 191 352 respectively for strategies 1, 2, and 3 listed
above. The total annual incremental costs for the cohort
were, respectively, $202 300 671, $112 580 535, and
$180 150 494. Sensitivity analyses showed that the cost
per case is highly dependent on the population incidence
of kernicterus and the RRR with each strategy, both of
which are currently unknown. In our model, annual cost
savings of $46 179 465 for the cohort would result with
strategy 2, if the incidence of kernicterus is high (1:10 000
births or higher) and the RRR is high (>0.7). If the
incidence is lower or the RRR is lower, then the cost per
case prevented ranged from $4 145 676 to as high as
$77 650 240.
Conclusions. Widespread implementation of these
strategies is likely to increase health care costs signifi-
cantly with uncertain benefits. It is premature to imple-
ment routine predischarge serum or transcutaneous bili-
rubin screening on a large scale. However, universal
follow-up may have benefits beyond kernicterus preven-
tion, which we did not include in our model. Research is
required to determine the epidemiology, risk factors, and
causes of kernicterus; to evaluate the effectiveness of
strategies intended to prevent kernicterus; and to deter-
mine the cost per quality-adjusted life year with any
proposed preventive strategy. Pediatrics 2004;114:917
924; kernicterus, cost-effectiveness, newborn, infant, jaun-
dice, cost, screening, bilirubin.
ABBREVIATIONS. CDC, Centers for Disease Control and Preven-
tion; AAP, American Academy of Pediatrics; RRR, relative risk
reduction.
R
ecently, there has been concern about a resur-
gence of kernicterus in the United States,
1
with
case reports of extremely high serum bilirubin
levels occurring in term or near-term infants. Al-
though there are no epidemiologic studies of ker-
nicterus and the population incidence of kernicterus
is unknown,
2,3
concern that its incidence might be
rising has led to a sentinel event alert issued by the
Joint Commission on Accreditation of Healthcare Or-
ganizations,
4
a report of 4 cases of kernicterus by the
Centers for Disease Control and Prevention (CDC) in
its Morbidity and Mortality Weekly Report,
5
and a state-
ment by the American Academy of Pediatrics (AAP)
2
intended to bring the issue of kernicterus to the
attention of the pediatric community. In the sentinel
event alert, the Morbidity and Mortality Weekly Report
and the AAP statement, several potential causes and
risk factors for the occurrence of kernicterus were
discussed. These documents also listed several po-
tential risk reduction strategies to ensure the early
detection and timely treatment of hyperbiliru-
binemia and thereby decrease the risk of kernicterus.
Some of the listed strategies include adherence to the
AAP Practice Guidelines for Management of Hyper-
bilirubinemia in the Healthy Term Newborn,
6
either
universal follow-up by a physician or a pediatric
nurse of all newborns within 24 to 48 hours of hos-
pital discharge or discharge and follow-up strategies
based on risk assessment, and plotting of predis-
charge serum or transcutaneous bilirubin values on a
percentile-based nomogram to identify and follow
up infants who are identified to be at risk for severe
hyperbilirubinemia. A recent AAP guideline about
From the *Department of Pediatrics, Medical University of South Carolina
Childrens Hospital, Charleston, South Carolina; and Center for Health
Policy and Research, University of Massachusetts Medical School, Worces-
ter, Massachusetts.
Accepted for publication Jul 15, 2004.
doi:10.1542/peds.2004-0583
This study was presented in part at the Pediatric Academic Societies Annual
Meeting; May 47, 2002; Baltimore, Maryland.
Reprint requests to (G.S.) MUSC Childrens Hospital, Room 664, Neonatal
Division, 165 Ashley Ave, PO Box 250917, Charleston, SC 29425. E-mail:
suresh@musc.edu
PEDIATRICS (ISSN 0031 4005). Copyright 2004 by the American Acad-
emy of Pediatrics.
PEDIATRICS Vol. 114 No. 4 October 2004 917
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the management of hyperbilirubinemia in the new-
born infant who is 35 weeks of gestation
7
has also
endorsed these strategies.
Currently, health care providers and health sys-
tems that are responsible for the care of newborn
infants before and immediately after hospital dis-
charge are under pressure to implement strategies
such as the ones listed above. However, although
these strategies seem logical and make sense intu-
itively, their effectiveness in reducing kernicterus is
unproved. Several of these strategies will increase
health care costs as a result of increased bilirubin
testing, a greater number of office or home nurse
visits, and an increased number of infants treated (a
consequence of a lowered treatment threshold).
Three of the strategies listed above are particularly
likely to involve increased spending on health care
resourcesuniversal follow-up after hospital dis-
charge, routine predischarge serum bilirubin testing
with selective follow-up, and routine predischarge
transcutaneous bilirubin testing with selective fol-
low-up. An assessment of the benefits, risks, and
costs of strategies to prevent kernicterus therefore is
necessary before implementing nationwide policy
changes. We undertook an incremental cost-effec-
tiveness analysis of these 3 kernicterus prevention
strategies compared with the current pattern of prac-
tice in the care of newborn infants.
METHODS
Cohort of Subjects
The subjects for this analysis were healthy, term (37 weeks
gestation or greater) infants who were being discharged from the
normal newborn nursery within 48 hours of an uncomplicated
vaginal birth. To estimate the number of infants who would be
contained in this cohort, from the 4 000 000 total live births per
year in the United States,
6
we subtracted 30% to account for births
occurring by cesarean section, preterm births, births with an ob-
vious setting for hemolysis (eg, Rh incompatibility), or other high
risk conditions. The remaining 2 800 000 infants (70% of all live
births) form the cohort for whom costs and outcomes were mod-
eled.
Structure of the Model
We constructed a decision analytic model to evaluate 3 differ-
ent strategies that are intended to prevent kernicterus and com-
pared them with the current practice of prevention and manage-
ment of jaundice in newborn infants, with each strategy to be
applied before the standard office visit at 2 weeks of age. We used
DATA 3.5 (TreeAge Software, Inc, Williamstown, MA) to struc-
ture the decision tree and estimate the total costs of each strategy.
One branch of this tree is depicted in Fig 1. The branch structures
for the other strategies modeled are identical to the depicted
branch; however, the transitional probabilities for each strategy
are different and shown in Table 1. We used a Microsoft Excel
spreadsheet to calculate the cost per case of kernicterus prevented.
The strategies that we compared are
1. Current management. Infants in this arm are treated according
to current practice patterns. After delivery and before hospital
discharge, physicians and nurses assess infants and determine
the need for serum bilirubin testing on the basis of a review of
clinical history and physical examination, including visual in-
spection of skin color. Clinical judgment and implicit assess-
ment of risk are used in determining the timing of postdis-
charge office visits or home visits by nurses before the 2-week
visit.
2. Universal follow-up 1 to 2 days after early discharge. In this
arm, after delivery and before hospital discharge, physicians
and nurses assess infants and determine the need for serum
bilirubin testing on the basis of a review of clinical history and
physical examination, including visual inspection of skin color.
Routine predischarge bilirubin testing is not performed. All
infants are seen within 2 days of discharge, either in the phy-
sicians office or at home by a nurse, as recommended in the
1994 guidelines of the AAP.
6
3. Routine predischarge serum bilirubin testing with selective
follow-up and laboratory testing. Under this strategy, in addi-
tion to the current management, all infants receive a serum
bilirubin test at the time of blood sampling for the neonatal
metabolic screen before discharge. This serum bilirubin is then
plotted on an hour-specific percentile on a nomogram that
guides decisions about follow-up and additional testing. Ac-
Fig 1. Decision tree depicting possible pathways for 1 strategy in the model. The same tree structure was used for all other strategies, with
variation in the transitional probabilities according to the strategy. PhotoRx, phototherapy.
918 COST-EFFECTIVENESS OF KERNICTERUS PREVENTION STRATEGIES
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cording to the recommendations of Bhutani et al,
8
infants
whose predischarge bilirubin value is greater than the hour-
specific 40th percentile value on the nomogram are scheduled
for either an office visit or a home nurse visit within 2 days of
discharge.
4. Routine predischarge transcutaneous bilirubin with selective
follow-up and laboratory testing. Under this strategy, in addi-
tion to the current management, all infants are tested with the
Bilichek transcutaneous bilirubinometer
9
before discharge. The
transcutaneous bilirubin value is plotted on the hour-specific
percentile on the nomogram developed by Bhutani et al.
8
The
percentile location of this value guides decisions about the need
for serum bilirubin testing before discharge and the scheduling
of follow-up office visits or home nurse visits.
Under each strategy, within 2 days of early discharge, each
infant would receive a follow-up office visit, a home visit by a
nurse, or no follow-up (either because of parental noncompliance
or because the first visit is intentionally scheduled at 2 weeks of
life, with telephone support in the interim). The early office visit or
home nurse visit is in addition to the standard 2-week visit that is
recommended by the AAP. The home visit by the nurse would, in
some cases, result in a referral to the physicians office for evalu-
ation by the primary care physician before the 2-week visit.
At the postdischarge office visit, the history and physical ex-
amination, including visual assessment of skin color, is used to
determine the need for serum bilirubin testing and other labora-
tory tests such as a hemogram, blood type, Coombs test, and
reticulocyte count. In addition, in all 3 strategies, the threshold for
laboratory testing is lowered, because authorities have empha-
sized the unreliability of visual estimation of bilirubin levels and
the need for a low threshold for measuring the serum biliru-
bin.
1,2,4,5,7
In addition, the knowledge of the infants predischarge
bilirubin percentile value (derived from the serum or transcuta-
neous bilirubin value) induces a lower threshold for laboratory
testing and additional follow-up. The serum bilirubin value will
guide decisions about the need for reassessment by the health care
provider in the subsequent day or 2, repeat serum bilirubin testing
to track a borderline bilirubin value (this is included under lab-
oratory testing in the model), and the need for treatment with
phototherapy. The availability of resources, comorbid conditions
in the infant (eg, dehydration), and local practice patterns would
guide decisions about whether phototherapy was provided at
home or in the hospital. Because the frequency of exchange trans-
fusion is low, we did not include it in the model.
Probabilities
The baseline estimates for probabilities used in the model are
listed in Table 1. For strategy 1, current practice, we based the
probabilities listed in Table 1 of an infants being seen in the office
or during a home visit on publications by Galbraith,
10
who re-
ported, using population-based data, that 32% of early-discharged
infants were seen by a health care provider within 2 days of
discharge, and on other publications from single institutions that
reported that one third to two thirds of early-discharged new-
borns do not receive the AAP-recommended follow-up visits.
11,12
Sixty percent of healthy newborns are reported to develop jaun-
dice,
6
and on a recent survey,
13
pediatricians reported checking
serum bilirubin levels in 55% of jaundiced newborns who are seen
in the office. Therefore, we used 0.33 (0.6 * 0.55) for the probability
of laboratory testing during an office visit. This estimate is con-
sistent with a report that 17% to 52% of infants in a large health
maintenance organization had at least 1 bilirubin level checked.
14
Meara et al
15
reported that 0.47% of all infants discharged early
were rehospitalized for jaundice. Madden et al
16
reported that
1.8% to 2.4% of all such infants were treated with hospital or home
phototherapy. Therefore, we adjusted the probabilities of labora-
tory testing and receiving phototherapy treatment in our model so
that 2% of the cohort infants under the current practice strat-
egy received phototherapy. We obtained the remaining probabil-
ities from interviews with pediatricians who represented 4 group
practices in Burlington, VT, about their practice patterns.
We estimated some of the probabilities for strategies 3 and 4
from the original articles describing the hour-specific bilirubin
nomogram
8
and the correlation between the transcutaneous bil-
irubinometry readings and serum bilirubin.
9
The remaining prob-
abilities are estimates on the basis of the first authors knowledge
about neonatal jaundice and its treatment and on discussions with
pediatric colleagues about likely pediatric practice changes in
response to promulgated prevention strategies. We assumed that
in all 3 prevention strategies, the threshold for treatment would be
lowered, because policies that promote aggressive screening for
jaundice and for risk of jaundice in combination with published
alerts from authorities about a resurgence of kernicterus are likely
to cause many health care providers to treat earlier in the course
of disease and at lower levels of bilirubin than with current
practice. The percentage of all cohort infants who received pho-
totherapy in the 4 pathways is as follows: current practice, 2.3%;
universal follow-up, 8.1%; predischarge serum bilirubin, 5.6%;
and predischarge transcutaneous bilirubin, 7.8%.
Costs
The baseline estimates for costs used in the model are listed in
Table 2. The costs are obtained by summing the individual costs of
the branches for each unique pathway in the decision analysis
model. We estimated costs from a modified societal perspective,
for the total number of liveborn infants per year in the United
States who would be eligible for the 3 preventive strategies. We
estimated all costs in 2002 dollars. We obtained provider charges
for laboratory tests for bilirubin, hemogram, blood typing, and
Coombs test from the central laboratory at Fletcher Allen Health
Care hospital (Burlington, VT). To this we added the costs for
supplies for blood sampling ($1.00 per infant) and 20 minutes of
nursing time (at an hourly rate of $24). We obtained the costs of
transcutaneous bilirubinometry from the company (Respironics,
Murrysville, PA) that markets Bilichek, the instrument tested by
Bhutani et al.
9
The cost of the bilirubinometer was $3995. We
assumed that 2 such instruments would be used for transcutane-
ous bilirubin tests in 8000 infants before becoming nonfunctional
or outdated by a newer model. The cost of the disposables
(Lensette tips) for each infant tested was $6.80. Therefore, the total
cost for each infant tested was $7.80. We obtained the charges for
an office visit ($50 per visit) from the charges for pediatric office
visits in Burlington, VT, by talking to local pediatricians. We
obtained the charges for home visits by skilled nurses from the
Visiting Nurses Association of Vermont ($95 per visit).
We obtained the hospital charges per day ($670 per day) from
the charges at Fletcher Allen Health Care hospital and assumed
that the average duration of hospitalization for an infant who is
TABLE 1. Probabilities Used for Modeling in Decision Tree
Pathways After Discharge
in Decision Tree
Current
Practice
Universal
Follow-up
Predischarge
Serum
Bilirubin
Predischarge
Transcutaneous
Bilirubin
Home nurse visit 12 d after discharge 0.2 0.2 0.1 0.1
Referred for office visit after home nurse visit 0.1 0.3 0.4 0.4
Undergoing laboratory testing after office visit 0.9 0.9 0.8 0.8
Hospitalized for phototherapy after laboratory testing 0.4 0.1 0.1 0.1
Treated with home phototherapy after laboratory testing 0.3 0.1 0.1 0.1
Office visit 12 d after discharge 0.3 0.7 0.5 0.6
Undergoing laboratory testing after office visit 0.33 0.5 0.5 0.6
Hospitalized for phototherapy after laboratory testing 0.05 0.1 0.1 0.1
Treated with home phototherapy after laboratory testing 0.05 0.1 0.1 0.1
Not examined by health care provider in the 2 days after discharge 0.5 0.1 0.4 0.3
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admitted for phototherapy is 2 days, thus yielding a total hospital
charge per admission of $1340. The charges for phototherapy are
assumed to be included in the hospital charges. For each hospital
admission, we estimated the attending physicians charges from
the charges of pediatricians who admit infants to Fletcher Allen
Health Care hospital ($84 per day). We obtained the charges for
home phototherapy ($134 per day) from Keene Medical store in
Burlington, VT, a private company that leases out home photo-
therapy units. We estimated that the average duration of treat-
ment for home phototherapy is 4 days, thus yielding total charges
of $536 per infant treated with home phototherapy. We estimated
that for each infant who receives home phototherapy, 1 additional
home nurse visit and 2 additional serum bilirubin tests would be
performed.
When we obtained charges instead of direct costs, we derived
the costs by applying a cost-to-charge ratio of 0.58, the Medicare
statewide average operating cost-to-charge ratio for an urban hos-
pital in Vermont.
17
For the home nurse visit, the home photother-
apy, and the transcutaneous measurement of bilirubin, we as-
sumed that the charge and the cost were identical. All costs are
expressed in 2002 dollars. We included only direct costs and did
not include indirect costs such as work-loss costs for the parents.
We based our estimate of the savings resulting from the pre-
vention of kernicterus on published data from the CDC on the
average lifetime direct and indirect costs per person of cerebral
palsy ($921 000 in 2003 dollars, $900 738 in 2002 dollars) and
mental retardation ($1 014 000 in 2003 dollars and $991 692 in 2002
dollars) discounted at 3%.
18
For purposes of comparison, these
more recent estimates are somewhat different from lifetime costs
for cerebral palsy ranging from $644 846 (at a 5% discount rate in
2002 dollars) to $1 533 272 (at a 2% discount rate in 2002 dollars)
reported by Waitzman et al
19
in 1992. We used $900 000 for the
lifetime cost for a child with kernicterus, assuming that the life-
time cost for a child with kernicterus would be similar to that of a
child with cerebral palsy or mental retardation.
Outcomes
As our primary outcome, we estimated the cost to prevent 1
case of kernicterus, by implementing each one of strategies 2, 3, or
4. We assumed that the effectiveness of each strategy in prevent-
ing kernicterus was similar. In the absence of data to determine
the relative risk reduction (RRR) with each strategy, we assumed
an RRR of 0.7 (ie, with each strategy, 70% of the cases of ker-
nicterus occurring with current practice would be prevented). We
estimated the incremental cost for the entire cohort with each of
these strategies by subtracting, from the cost of a given strategy,
the cost of current management as well as the savings resulting
from kernicterus cases prevented ($900 000 multiplied by the
number of kernicterus cases prevented). We divided this incre-
mental cost by the estimated number of cases of kernicterus pre-
vented per year to obtain the cost per case prevented.
Sensitivity Analysis
The true population incidence of kernicterus is unknown.
2,3
Therefore, in modeling the cost per case of kernicterus prevented,
we performed 1-way sensitivity analyses by varying the incidence
of kernicterus from 1:10 000 healthy term live births to 1:500 000
such births and by varying the RRR from 1.0 to 0.1.
RESULTS
The cost to prevent 1 case of kernicterus using our
base-case estimates in the 3 preventive strategies
compared with current practice is shown in Table 3.
This cost was highest with the strategy of universal
early follow-up ($10 321 463) and lowest with the use
of routine predischarge serum bilirubin screening
($5 743 905). The results of the 1-way sensitivity anal-
ysis across a range of estimates of the incidence of
kernicterus, with a fixed RRR of 0.7 are shown in
Table 4. There was a wide variation in the cost to
prevent 1 case of kernicterus. If the kernicterus inci-
dence is high (1:10 000 births), then the routine pre-
discharge serum bilirubin strategy would result in
negative costs (ie, annual cost savings of $46 179 465
for the cohort). However, in all other situations, the
cost per case prevented ranged from $109 135 (with a
high incidence of kernicterus) to $55 207 314 (with a
low incidence of kernicterus). The results of a 1-way
sensitivity analysis across a range of RRR assump-
TABLE 2. Estimates of Costs in 2002 Dollars
Item Estimated
Charges
Estimated
Costs
Comments
Office visit $50.00 $29.00
Home visit by nurse $95.00
Serum bilirubin $20.00 $11.60 Laboratory charges $10.66; 20 min nursing
time for blood draw $8.00; (at 24/h);
Supplies $1.00
Hemogram $14.50 $8.41
Blood typing $41.00 $23.78
Coombs test $30.45 $17.66
Transcutaneous bilirubin $7.80 2 Bilichek units, each at $3995 used for 8000
infants $1.00, Lemsette tips, box of 50 at
$3.40 $6.80 each
Hospital charges $1340.00 $777.20 $670 per day for 2 d
Physician charges in hospital $168.00 $97.44 $84 per day for 2 d
Home phototherapy $536.00 $134 per day
Nurse visit during phototherapy $95.00 1 extra nurse visit during phototherapy
Bilirubin testing during home phototherapy $40.00 $23.20 2 bilirubin tests during home phototherapy
Bilirubin testing in hospital $40.00 $23.20 2 bilirubin tests during hospital phototherapy
TABLE 3. Annual Cost to Prevent 1 Case of Kernicterus at an Annual Incidence of 1:100 000 Healthy Term Births and RRR of 0.7
Strategy Incremental
Annual Cost for Cohort
Over Current Practice,* $
No. of Additional
Cases Prevented Per Year
Cost Per Case
Prevented, $
Universal follow-up 202 300 671 20 10 321 463
Predischarge serum bilirubin 112 580 535 20 5 743 905
Predischarge transcutaneous bilirubin 180 150 494 20 9 191 352
* Cost for the cohort from current practice $152 392 631.
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tions (with a fixed kernicterus incidence of 1:100 000
live births) are shown in Table 5. Estimates of the
cost per case prevented ranged from $3 750 733 to
$77 650 240 when RRR was varied from 1.0 to 0.1,
respectively, across the 3 strategies. In all situations,
at comparative incidence and relative risk figures,
the highest costs resulted from the universal fol-
low-up strategy and the lowest from the predis-
charge serum bilirubin strategy.
DISCUSSION
In response to a concern about an increase in the
incidence of kernicterus in the United States, several
authorities, including the AAP, have suggested that
increased surveillance or screening be performed for
neonatal hyperbilirubinemia.
1,2,4,5
Although the re-
cent AAP guideline
7
stated that one of its aims was to
reduce excessive cost and waste, it did not include
any estimates of cost-effectiveness. Instead, in this
guideline, the AAP Subcommittee on Neonatal Hy-
perbilirubinemia repeated its previous recommenda-
tion
2
that additional research be conducted to deter-
mine the incidence and prevalence of kernicterus in
the US population and to quantify the risk, benefits,
and costs of various strategies aimed at preventing
kernicterus. Our study, in which we modeled the
TABLE 4. One-Way Sensitivity Analysis of Cost Per Case Prevented Across a Range of Incidence of Kernicterus*
Strategy Annual Kernicterus
Incidence
No. of Cases
Prevented
Per Year
Annual Cost for
Entire Cohort, $
Cost Per Case
Prevented, $
Universal follow up 10 000 196 43 540 671 222 146
50 000 39 184 660 671 4 710 731
100 000 20 202 300 671 10 321 463
250 000 8 212 884 671 27 153 657
500 000 4 216 412 671 55 207 314
Predischarge serum bilirubin 10 000 196 46 179 465 235 610
50 000 39 94 940 535 2 421 952
100 000 20 112 580 535 5 743 905
250 000 8 123 164 535 15 709 762
500 000 4 126 692 535 32 319 524
Predischarge transcutaneous bilirubin 10 000 196 21 390 494 109 135
50 000 39 162 510 494 4 145 676
100 000 20 180 150 494 9 191 352
250 000 8 190 734 494 24 328 379
500 000 4 194 262 494 49 556 759
* An RRR of 0.7 is assumed for each strategy.
Number of healthy term live births out of which 1 case of kernicterus occurs.
TABLE 5. One-Way Sensitivity Analysis of Cost Per Case Prevented Across a Range of RRRs for Each Preventive Strategy*
Strategy RRR No. of Cases
Prevented Per Year
Annual Cost for
Entire Cohort, $
Cost Per Case
Prevented, $
Universal follow-up 1 28 194 740 671 6 955 024
0.9 25 197 260 671 7 827 804
0.8 22 199 780 671 8 918 780
0.7 20 202 300 671 10 321 463
0.6 17 204 820 671 12 191 707
0.5 14 207 340 671 14 810 048
0.4 11 209 860 671 18 737 560
0.3 8 212 380 671 25 283 413
0.2 6 214 900 671 38 375 120
0.1 3 217 420 671 77 650 240
Predischarge serum bilirubin 1 28 105 020 535 3 750 733
0.9 25 107 540 535 4 267 482
0.8 22 110 060 535 4 913 417
0.7 20 112 580 535 5 743 905
0.6 17 115 100 535 6 851 222
0.5 14 117 620 535 8 401 467
0.4 11 120 140 535 10 726 834
0.3 8 122 660 535 14 602 445
0.2 6 125 180 535 22 353 667
0.1 3 127 700 535 45 607 334
Predischarge transcutaneous bilirubin 1 28 172 590 494 6 163 946
0.9 25 175 110 494 6 948 829
0.8 22 177 630 494 7 929 933
0.7 20 180 150 494 9 191 352
0.6 17 182 670 494 10 873 244
0.5 14 185 190 494 13 227 892
0.4 11 187 710 494 16 759 866
0.3 8 190 230 494 22 646 487
0.2 6 192 750 494 34 419 731
0.1 3 195 270 494 69 739 462
* A kernicterus incidence of 1:100 000 healthy term live births is assumed with each strategy.
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cost-effectiveness of 3 potential risk reduction strat-
egies listed by these authorities, partially fulfills this
recommendation.
With each of these strategies, we modeled the
pathways of decision making and probabilities that
are depicted in Fig 1. These are only some of the
pathways possible, and several other patterns of test-
ing, treating, and following up are possible. For ex-
ample, pediatricians and nurses could use transcuta-
neous bilirubinometers to assess infants in their
offices or at home in addition to the in-hospital use of
this technique. In some areas, the nurse performing
the home visit could, if necessary, draw a serum
bilirubin sample. A clinical risk assessment using
demographic factors, features in the maternal and
perinatal history, and physical examination such as
described by Newman et al
7,20
could be performed as
a substitute for or in addition to 1 of the strategies
modeled by us. One appealing strategy that is likely
not to lead to increased costs is the use of the man-
datory early follow-up visit as a replacement for the
2-week visit instead of being an additional visit.
However, the impact of this strategy on kernicterus
as well as on other outcomes such as breastfeeding
success, hypernatremic dehydration, and other early
neonatal problems has to be assessed before imple-
menting it. The likely compliance of parents with this
strategy also has to be assessed.
Our study has several limitations. Although we
used published data as far as possible to obtain the
transitional probabilities for current practice and the
3 strategies modeled, some of the probabilities used
in the model were derived from interviews with
pediatricians in Burlington, VT, and pediatric prac-
tice patterns probably vary widely across the United
States. The change in practice pattern in response to
any strategy suggested by the AAP is also likely to
vary widely across the country. More rigorous, na-
tionwide data on the likely patterns of surveillance
and management of hyperbilirubinemia by pediatri-
cians and family practitioners in response to the AAP
guidelines are required to strengthen the reliability
of our model. The cost per case of kernicterus pre-
vented reported in our article may be an underesti-
mation because of 2 reasons. First, we did not include
indirect costs in our estimation of costs (except in the
estimate of lifetime costs of kernicterus). Second,
some of our cost estimates may be lower than actual
nationwide costs. A more rigorous determination of
costs is required to strengthen the reliability of the
costs component of the model. Finally, we did not
model other benefits that might result from fol-
low-up office or home nurse visits, such as improved
lactation and decrease in dehydration. Quantifying
these benefits and including them in the model
would alter the cost-effectiveness reported in our
study.
A key problem with any attempt to determine the
cost-effectiveness of strategies to prevent kernicterus
is the unknown population incidence of kernicter-
us.
2,3
In data from a large health maintenance orga-
nization published by Newman et al,
14
1 infant in
10 000 had a serum bilirubin of 30 mg/dL, but
none of the 11 infants identified in the study had
kernicterus on follow-up.
21
In data from the ker-
nicterus registry published by Johnson,
1
90 cases
were collected over 16 years. If we assume that only
ine quarter of all kernicterus cases were reported to
this registry, with 4 million births per year in the
United States, this yields an estimated incidence of 1
case of kernicterus per 178 000 live births. In our
base-case estimate (Table 3), we used an annual in-
cidence of 1 case of kernicterus per 100 000 healthy
term live births. Because the true incidence of ker-
nicterus may be lower or higher than this, we also
performed a 1-way sensitivity analysis using a range
of estimates from 1:10 000 to 1:500 000 healthy term
live births (Table 4). In a recent report of preliminary
data from New Jersey,
22
the CDC reported an inci-
dence of 82 cases of kernicterus per 100 000 live
births (identified using International Classification of
Diseases, Ninth Revision codes in all infants, not just
healthy term infants), an incidence that is encom-
passed within our range of estimates. Once these
preliminary data are confirmed and restricted to
healthy term newborns, they will be valuable in re-
fining the cost-effectiveness of kernicterus preven-
tion strategies.
No data are available on the efficacy or effective-
ness of any of the suggested strategies in preventing
kernicterus. The ideal study design to assess efficacy
for each strategy would be a randomized, controlled
trial of screening and follow-up, such as the one done
for neonatal cystic fibrosis screening.
23
In the absence
of such evidence of efficacy, we assumed an optimis-
tic relative risk reduction of 0.7 (ie, 70% of the cases
of kernicterus currently occurring would be pre-
vented by each of the strategies). We emphasize that
this RRR refers to the prevention strategy as applied
to a population of newborns, not to the treatment of
jaundice in an individual patient. Although ker-
nicterus in an individual healthy term infant is com-
pletely preventable, a prevention program applied to
a population of newborns is unlikely to eliminate all
cases of kernicterus in that population because the
effectiveness of such an intervention is the product of
its efficacy, compliance, and penetration,
24
and there
are often deficiencies in compliance and penetration.
For example, some of the cases of kernicterus that
currently occur are ascribed to deficiencies in health
services after hospital discharge, such as delays in
obtaining an office appointment for a jaundiced in-
fant, failure to check a bilirubin level in a jaundiced
infant, failure to recognize risk factors for severe
hyperbilirubinemia, reliance on exposure to sunlight
as a treatment for jaundice, and failure to treat hy-
perbilirubinemia at recommended levels.
1,2,4,5
If such
deficiencies persist after implementing predischarge
prevention strategies, then cases of kernicterus
would continue to occur. Increased bilirubin testing
before hospital discharge is unlikely to prevent such
cases and would represent wasted health care dol-
lars.
Also, implementing a surveillance or screening
strategy before discharge may induce a false sense of
reassurance and thus alter the behavior of health care
providers, perhaps by making them less vigilant. The
false-negative rate (sensitivity) of the percentile-
922 COST-EFFECTIVENESS OF KERNICTERUS PREVENTION STRATEGIES
at Indonesia:AAP Sponsored on June 20, 2014 pediatrics.aappublications.org Downloaded from
based prediction method recommended by Bhutani
et al
8
is unknown. This might result in the develop-
ment of kernicterus in some infants who, with cur-
rent practice, would have been detected and treated
in time. Therefore, with each of these strategies, there
is a possibility that the degree of risk reduction may
not be as high as 0.7, and there may possibly even be
an increase in risk, with an increase in the number of
cases of kernicterus compared with the current inci-
dence. We also made an assumption that each of the
strategies modeled would be equally effective in
achieving this RRR. The effectiveness and, conse-
quently, the cost-effectiveness of each of these strat-
egies may vary from each other in different settings
across the country.
With our baseline assumptions and estimates and
keeping in mind the limitations of the data, we found
that the cost to prevent 1 case of kernicterus using the
3 strategies that we modeled ranged from $5 700 000
to $10 000 000, depending on the strategy used. Con-
siderable cost savings ($46 000 000 for the cohort
annually) would result from routine predischarge
serum bilirubin screening if the incidence of ker-
nicterus were high (1:10 000 births) and the preven-
tive program were highly effective (RRR of 0.7).
However, with lower incidence rates and lower RRR
estimates, the cost to prevent 1 case ranged from
$4 100 000 to as high as $78 000 000. Two key drivers
of these wide ranges of costs are the uncertainty in
the degree of risk reduction (ie, the uncertainty about
the number of cases of kernicterus prevented with
each strategy) and the population incidence of ker-
nicterus. Our results provide a framework with
which to evaluate the benefits, costs, and risks of 3
potential preventive strategies for kernicterus and
that can be applied to other potential strategies as
well. When allocating resources to improve health
care outcomes, policy makers should keep these
costs and uncertainties in mind.
We emphasize that our results do not suggest that
attempts should not be made to eliminate kernicterus
or that kernicterus is not a disease worth preventing.
They do suggest, however, that it is premature to
implement large-scale routine bilirubin screening (ei-
ther serum or transcutaneous) before hospital dis-
charge because of the potential for high costs, uncer-
tain effectiveness, and the uncertain population
incidence of kernicterus. Before widespread imple-
mentation, the benefits and the lack of risks of such
screening first should be confirmed by rigorously
testing these strategies on a smaller scale. Because
universal follow-up within 48 hours of early dis-
charge may have benefits in addition to kernicterus
prevention, such as improved breastfeeding and pre-
vention of dehydration, we speculate, pending quan-
tification of these benefits, that this strategy might
still prove to be cost-effective. It is also reasonable to
implement other preventive strategies that are rec-
ommended by the AAP and other authorities,
1,2,4,5
even in the absence of rigorous proof of effective-
ness, as they are unlikely to increase health care costs
significantly and are unlikely to be harmful. These
include a predischarge risk assessment that is based
on clinical risk factors
20
; introduction of policies and
procedures that allow nurses to order bilirubin test-
ing for jaundiced newborns and that specifically
cover the nurses role, documentation, charting re-
quirements, and monitoring of jaundice predis-
charge; provision to parents of adequate verbal and
written information about newborn infants and jaun-
dice; and provision of adequate equipment to test for
and treat jaundice.
Additional research is required to understand the
epidemiology of kernicterus, identify causes and risk
factors for kernicterus, and determine the efficacy of
proposed strategies to decrease kernicterus. Research
is also required to determine the long-term use of
health care resources and costs of caring for children
with kernicterus as well as the quality of life in
infants who survive kernicterus. With such informa-
tion, a more comprehensive measure of cost-effec-
tiveness, such as the cost per quality-adjusted life
year, can be calculated.
REFERENCES
1. Johnson LH, Bhutani VK. System based approach to management of
neonatal jaundice and prevention of kernicterus. J Pediatr. 2002;140:
396403
2. American Academy of Pediatrics Subcommittee on Neonatal Hyperbi-
lirubinemia. Neonatal jaundice and kernicterus. Pediatrics. 2001;108:
763765
3. Newman TB, Maisels JM. Less aggressive treatment of neonatal jaun-
dice and reports of kernicterus: lessons about practice guidelines. Pedi-
atrics. 2000;105:242245
4. Joint Commission on Accreditation of Healthcare Organizations. Senti-
nel Event Alert. Oak Brook Terrace, IL: Joint Commission on Accredita-
tion of Healthcare Organizations; 2001
5. Centers for Disease Control and Prevention. Kernicterus in full term
infantsUnited States, 19941998. MMWR Morb Mortal Wkly Rep. 2001;
50:491494
6. American Academy of Pediatrics. Provisional committee for quality
improvement and subcommittee on hyperbilirubinemia. Practice
parameter: management of hyperbilirubinemia in the healthy term
newborn. Pediatrics. 1994;94:11221132
7. American Academy of Pediatrics. Provisional committee for quality
improvement and subcommittee on hyperbilirubinemia. Pediatrics.
2004;114:297316
8. Bhutani VK, Johnson L, Sivieri EM. Predictive ability of a pre-discharge
hour-specific serum bilirubin for subsequent significant hyperbiliru-
binemia in healthy term and near-term newborns. Pediatrics. 1999;103:
614
9. Bhutani VK, Gourley GR, Adler S, Kreamer B, Dalin C, Johnson LH.
Noninvasive measurement of total serum bilirubin in a multiracial
pre-discharge newborn population to assess the risk of severe hyperbi-
lirubinemia. Pediatrics. 2000;106(2). Available at: www.pediatrics.org/
cgi/content/full/106/2/e17
10. Galbraith AA, Egerter SA, Marchi KS, Chavez G, Braveman PA. New-
born early discharge revisited: are California newborns receiving rec-
ommended postnatal services? Pediatrics. 2003;111:364371
11. Maisels MJ, Kring E. Early discharge from the newborn nurseryeffect
on scheduling of follow-up visits by pediatricians. Pediatrics. 1997;100:
7274
12. Lieu TA, Wikler C, Capra AM, Martin KE, Escobar GJ, Braveman PA.
Clinical outcomes and maternal perceptions of an updated model of
perinatal care. Pediatrics. 1998;102:14371444
13. Petrova A, Mehta R, Ostfeld B, Scharf R, Hegyi T. New Jersey pedia-
tricians hyperbilirubinemia and kernicterus practice survey. Pediatr
Res. 2004;55(suppl):378A (abstr)
14. Newman TB, Escobar GB, Gonzales VM, Armstrong MA, Gardner MN,
Folck BF. Frequency of neonatal bilirubin testing and hyperbiliru-
binemia in a large health maintenance organization. Pediatrics. 1999;104:
11981203
15. Meara E, Kotagal U, Atherton HD, Lieu TA. Impact of early newborn
discharge legislation and early follow-up visits on infant outcomes in a
state medicaid population. Pediatrics. 2004;113:16191627
ARTICLES 923
at Indonesia:AAP Sponsored on June 20, 2014 pediatrics.aappublications.org Downloaded from
16. Madden JM, Soumerai SB, Lieu TA, Mandl KD, Zhang F, Ross-Degnan
D. Length-of-stay policies and ascertainment of postdischarge problems
in newborns. Pediatrics. 2004;113:4249
17. Centers for Medicare & Medicaid Services (CMS), HHS. Medicare
program; changes to the hospital inpatient prospective payment sys-
tems and fiscal year 2003 rates. Final rule. Fed Regist. 2002;67:4998150289
18. Centers for Disease Control and Prevention. Economic costs associated
with mental retardation, cerebral palsy, hearing loss and vision impair-
mentUnited States 2003. MMWR Morb Mortal Wkly Rep. 2004;53:5759
19. Waitzman NJ, Scheffler RM, Romano PS. The Cost of Birth Defects:
Estimates of the Value of Prevention. Lanham, MD: University Press of
America; 1996:4
20. Newman TB, Xiong B, Gonzales VM, Escobar GJ. Prediction and pre-
vention of extreme neonatal hyperbilirubinemia in a mature health
maintenance organization. Arch Pediatr Adolesc Med. 2000;154:11401147
21. Newman TB, Liljestrand P, Escobar GJ. Infants with bilirubin levels of
30 mg/dL or more in a large managed care organization. Pediatrics.
2003;111:13031311
22. Centers for Disease Control and Prevention. Kernicterus research activ-
itiesUMDNJ-Robert Wood Johnson Medical School Kernicterus Re-
search and Prevention Center. Available at: www.cdc.gov/ncbddd/
dd/kernres.htm. Accessed July 1, 2004
23. Farrell PM, Kosorok MR, Rock MJ, et al. Early diagnosis of cystic
fibrosis through neonatal screening prevents severe malnutrition and
improves long-term growth. Wisconsin Cystic Fibrosis Neonatal
Screening Study Group. Pediatrics. 2001;107:113
24. Teutsch SM, Haddix AC. Decision analysis for public health. In: Haddix
AC, Teutsch SM, Shaffer PA, Dunet DO, eds. Prevention Effectiveness. A
Guide to Decision Analysis and Economic Evaluation. New York, NY:
Oxford University Press; 1996:52
EXPERT WITNESSES?
A new study raises significant questions over the medical findings of some
doctors acting as expert witnesses in asbestos liability lawsuits. In the study, an
independent panel of doctors reviewed 492 chest X-rays that had been submitted
by plaintiffs lawyers in asbestos lawsuits. They found that only a small fraction
indicated possible asbestos-related lung damage. That was in stark contrast to the
conclusions of the doctors who originally read the X-rays after being retained by
lawyers representing people who were claiming injury. Those doctors found that
96 percent of the X-rays showed possible damage. It was astonishing, said Dr
Joseph N. Gitlin, an associate professor of radiology at Johns Hopkins Medical
Institutions, who is the lead author of the study, which will be published in
Academic Radiology, a journal for university radiologists. Although Dr Gitlin has
served as a consultant for lawyers defending companies from asbestos claims, he
said he was not paid to conduct the study. . . . Studies have shown that doctors
looking at X-rays typically differ a third of the time in their interpretation. . . . In an
accompanying editorial in the same issue of the journal, 2 doctors not involved in
the study say the findings raise questions about the integrity of some doctors who
serve as expert witnesses.
Reed A. New York Times. August 4, 2004
Noted by JFL, MD
924 COST-EFFECTIVENESS OF KERNICTERUS PREVENTION STRATEGIES
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DOI: 10.1542/peds.2004-0899
2004;114;917 Pediatrics
Gautham K. Suresh and Robin E. Clark
Newborn Infants
Cost-Effectiveness of Strategies That Are Intended to Prevent Kernicterus in

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