RESEARCH ARTICLE

The Utility of Inpatient Rebound Bilirubin

Levels in Infants Readmitted After Birth
Hospitalization for Hyperbilirubinemia
AUTHORS
abstract Adam Berkwitt, MD, Rachel Osborn, MD,
Matthew Grossman, MD
BACKGROUND AND OBJECTIVES: There are few data evaluating the role of
inpatient rebound bilirubin levels in the management of infants readmitted after Department of Pediatrics, Yale University School
of Medicine, New Haven, Connecticut
their birth hospitalization for indirect hyperbilirubinemia. The goal of the present
study was to evaluate the clinical utility of inpatient rebound bilirubin levels KEY WORDS
jaundice, infant, readmission, phototherapy,
within this patient population. length of stay
METHODS: A retrospective cohort study was conducted of 226 infants ABBREVIATION
readmitted after their birth hospitalization for indirect hyperbilirubinemia. Data AAP: American Academy of Pediatrics
from 130 infants with rebound bilirubin levels drawn at a mean of 6.1 2.4 hours www.hospitalpediatrics.org
doi:10.1542/hpeds.2014-0074
after discontinuation of phototherapy were compared with data from 96 infants
Address correspondence to Adam Berkwitt,
without rebound bilirubin levels. The primary outcome was readmission to the MD, Department of Pediatrics, Yale University
hospital, and secondary outcomes included length of stay and discharge time. School of Medicine, 333 Cedar St, PO Box
A subgroup analysis compared characteristics of children who required repeat 208064, New Haven, CT 06520-8064. E-mail:
adam.berkwitt@yale.edu
phototherapy versus those who did not.
HOSPITAL PEDIATRICS (ISSN Numbers: Print,
RESULTS: Overall, 5 of 130 patients from the rebound group were readmitted 2154 - 1663; Online, 2154 - 1671).
compared with 4 of 96 patients from the no-rebound group (P = .98). Length of Copyright 2015 by the American Academy of
stay was significantly longer for patients with rebound bilirubin levels (27.7 vs Pediatrics

23.2 hours; P = .001). Patients with bilirubin levels lowered to 14 mg/dL were FINANCIAL DISCLOSURE: The authors have
less likely to receive repeat phototherapy than those with levels >14 mg/dL (2 of indicated they have no financial relationships
129 vs 12 of 97; P = .001). relevant to this article to disclose.

FUNDING: No external funding.

CONCLUSIONS: Early inpatient rebound bilirubin levels do not successfully
predict which patients will require hospital readmission for repeat phototherapy. POTENTIAL CONFLICT OF INTEREST: The
authors have indicated they have no potential
Children with bilirubin levels lowered to 14 mg/dL with phototherapy are conflicts of interest to disclose.
unlikely to receive repeat phototherapy.

The 2004 American Academy of Pediatrics (AAP) guideline on the evaluation and
management of hyperbilirubinemia in the newborn infant states that discharge
from the hospital need not be delayed to observe the infant for rebound bilirubin
levels.1 Despite this recommendation, many pediatricians obtain early (48 hours)
rebound bilirubin levels after discontinuation of phototherapy. There is currently
a lack of robust data addressing the value of early (<12 hours) inpatient rebound
bilirubin levels; much of the previous research used to create the AAP guideline
focused on rebound bilirubin levels that were drawn, on average, 12 hours from
the cessation of phototherapy.26

Although recent research has focused on attempts to improve adherence to AAP

guidelines, it is also necessary to provide stronger evidence evaluating the effects
of early inpatient rebound bilirubin levels.7 The present study assessed the clinical
utility of rebound bilirubin levels for infants readmitted with hyperbilirubinemia

74 | VOLUME 5 ISSUE 2 www.hospitalpediatrics.org

 HOSPITAL Pediatrics
after their birth hospitalization. The fol-
lowing outcomes were assessed: sub-
sequent hospital readmission rates,
length of stay, discharge time, and
re-initiation of phototherapy during a
current admission. We hypothesized
that inpatient rebound bilirubin levels
would not affect readmission rate.
METHODS
We identified subjects readmitted to
YaleNew Haven Childrens Hospital,
a tertiary care center with 3800 new-
borns delivered annually. The medi-
cal records database was reviewed
for infants <10 days of age with
International Classification of Diseases,
Ninth Revision, codes for a principal
diagnosis of jaundice and a principal
or secondary procedure of photo-
therapy between January 2007 and
April 2014. Patients were eligible for
inclusion if they had a gestational age
35 weeks and were readmitted from
the newborn nursery for phototherapy
treatment of indirect hyperbilirubine-
mia. Exclusion criteria consisted of:
history of phototherapy in the first
24 hours of life, admission to the ICU,
exchange transfusion, direct hyper-
bilirubinemia, and evidence of sepsis
at time of admission. If a child had >1
hospitalization with a primary diagno-
sis of jaundice, only the first encounter
was included in the analysis.
Data from children who had inpatient
rebound bilirubin levels checked <12
hours after phototherapy cessation
(rebound group) were compared with
those who did not have repeat levels
drawn (no-rebound group). The deci-
sion to check a rebound bilirubin level
and the timing of this investigation were
determined by the attending pediatri-
cian. Decisions regarding initiation of
phototherapy were based on the nomo-
gram from the 2004 AAP guidelines
AN OFFICIAL JOURNAL OF THE AMERICAN ACADEMY OF PEDIATRICS
and the 2009 update on the evaluation
and management of hyperbilirubine-
mia in the newborn infant.1,8 Infants
were stratified into low-, medium-, or
high-risk groups based on presence
of risk factors for hyperbilirubinemia/
kernicterus. Decisions to implement
phototherapy were based on single
serum bilirubin levels obtained at the
time of admission and the correspond-
ing light level based on hours of life on
final analysis (Fig 1). Overall, 130 (58%)
the nomogram.8 All patients requiring
phototherapy received triple light ther-
apy, and no changes in the dosage of
phototherapy occurred during the study
period.
The primary outcome was readmis-
sion for repeat phototherapy within
72 hours of discharge. Secondary out-
comes include length of inpatient stay,
duration of phototherapy, and hospital
discharge time. A separate analysis
compared characteristics of patients
who required repeat phototherapy
(either with readmission or on the
same admission) with those patients
who did not. Continuous variables in
the 2 groups were compared by using
FIGURE 1 Study design.
the 2-sample t test. We analyzed cat-
egorical data by using either the 2
test or Fischers exact test as dictated
by sample size. The Yale University
Human Investigation Committee pro-
vided approval for the review of all
medical records.
RESULTS
There were 252 infants identified in the
search, and 226 were included in the
of the 226 patients had a rebound bili-
rubin level checked a mean of 6.1 2.4
hours from phototherapy cessation,
and 96 (42%) of 182 patients had no
rebound level checked. There were no
significant differences in the baseline
characteristics between the 2 groups
(Table 1). Table 2 displays the biliru-
bin levels at phototherapy initiation
and cessation, as well as the duration
of phototherapy. Initial bilirubin levels
were higher in the rebound group com-
pared with the no-rebound group, and
they were also higher at time of light
cessation. The rebound group had a
significantly shorter duration of photo-
therapy (15.1 vs 17.7 hours; P = .008).
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 HOSPITAL Pediatrics AN OFFICIAL JOURNAL OF THE AMERICAN ACADEMY OF PEDIATRICS

TABLE 1 Baseline Characteristics phototherapy, whereas 12 (12.4%) of

Characteristic Rebound Group (n = 130) No-Rebound Group (n = 96) Difference P 97 whose bilirubin level at cessa-
Age, da 4.6 (4.34.8) 4.3 (4.14.6) 0.3 .24 tion was >14 mg/dL required repeat
Gestational agea,b 38.4 (38.138.3) 38.2 (37.938.5) 0.2 .34 phototherapy (P = .001).
Ethnicity/race, (%) .86
White 70 (54) 49 (51) ***
DISCUSSION
Black 12 (9) 10 (10) ***
Asian 12 (9) 9 (9) *** To date, there is a limited amount of
Hispanic/Latino 26 (20) 23 (25) *** research addressing the potential clin-
Other 10 (8) 5 (5) ***
ical utility of early (<12 hours) rebound
Gender, (%) .71
Male 72 (55) 55 (59) *** bilirubin levels.911 In 1999, Del Vecchio
Female 58 (45) 40 (41) *** et al9 analyzed 48 infants with rebound
Birth weight, kga 3.26 (3.163.36) 3.22 (3.133.31) 0.04 .54
Infant feeding, (%) .27
levels ranging from 6 to 8 hours and
Breast 104 (80) 68 (71) *** found a decrease in average rebound
Formula 5 (4) 7 (7) *** bilirubin level compared with level at
Combination 21 (16) 21(22) ***
All risk of 34 (26) 30 (31) *** .1
cessation of phototherapy. A 2002
hemolysisc, (%) retrospective analysis by Al-Saedi10
a
Mean (95% confidence interval). evaluated 301 infants with rebound
bilirubin level times averaging 8.3
b
Rounded to the nearest week.
c
Defined as ABO incompatibility, positive Coombs test result, reticulocytosis >5%, cephalohematoma,
and significant bruising. 5.3 hours and found no significant
increase in early rebound bilirubin
Nine (4%) of 226 children in the versus mean bilirubin levels at
levels. Our study is in line with this
cohort were readmitted to the hospi- the time of phototherapy cessation
previous research, as we reported
tal for additional phototherapy within (13.7 mg/dL; P = .1). Five of the
no significant increase in early inpa-
72 hours of discharge, with no signifi- 130 children in the rebound group
tient rebound bilirubin levels drawn at
cant difference in readmission rates received repeat phototherapy on the
a mean of 6.1 2.4 hours compared
between the rebound and no-rebound same admission. Overall, 14 (6.2%)
with the level at phototherapy cessa-
groups (Table 3). When only children of 226 patients required repeat photo-
tion. However, to our knowledge, our
with risk factors for hemolysis were therapy (9 readmitted and 5 re-initiated
study is the first to directly compare
included in the analysis, 1 (2.9%) of at same admission). Only 2 of these
patients with early rebound bilirubin
34 patients from the rebound group 14 patients adhered to the AAP guide-
levels versus those without rebound
were readmitted versus 3 (10%) of 30 line of lowering bilirubin levels to
levels, specifically addressing differ-
from the no-rebound group (P = .3). 14 mg/dL before discontinuation of
ences in clinical outcomes such as
Mean length of stay was significantly phototherapy. Further analysis revealed
readmission rates, length of stay, and
increased in the rebound group, and that patients in the no-rebound group
discharge timing.
mean hospital discharge time was were significantly more likely to have
significantly later in the rebound bilirubin levels lowered to 14 mg/dL Early inpatient rebound bilirubin levels
group. compared with the rebound group were checked in a majority of infants
(66 of 96 vs 63 of 130; P = .003). at our institution, and this practice did
Within the rebound group, there was Overall, 2 (1.6%) of 129 infants not successfully prevent readmission.
no significant difference in mean whose bilirubin level at cessation However, within the rebound group,
rebound bilirubin levels (13.4 mg/dL) was 14 mg/dL required repeat 5 (3.8%) of 130 patients underwent

TABLE 2 Bilirubin Levels and Duration of Phototherapy

Variable Rebound Group (n = 130) No-Rebound Group (n = 96) Difference P
Mean bilirubin at phototherapy initiation, mg/dL 19.5 18.8 0.7 .03
Mean bilirubin at phototherapy cessation, mg/dL 13.7 13.0 0.7 .008
Mean duration of phototherapy, h 15.1 17.7 -3.3 .008
Total no. of patients with bilirubin level 14 mg/dL at 63 (48) 66 (69) (21) .003
phototherapy cessation, (%)

76 | VOLUME 5 ISSUE 2 www.hospitalpediatrics.org

 HOSPITAL Pediatrics
TABLE 3 Readmissions and Length of Stay
Variable
Total no. of readmissions, (%)
Mean length of stay for current admission, h
Mean discharge time for current admission
Total no. of patients discharged before
11:00 AM, (%)
a
Fishers exact test.
repeat phototherapy during the same
admission. Of these 5 infants, 1 had
a cephalohematoma, and 2 had ABO
incompatibility with negative results
on the Coombs test. Importantly, all of
these patients had phototherapy halted
at a level >14 mg/dL, with bilirubin levels
of 14.7, 15.9, 16.7, 16.8, and 17.6 mg/dL
at phototherapy cessation. In cases in
which phototherapy was initially con-
tinued to reach the AAP recommenda-
tion of 14 mg/dL, all rebound bilirubin
levels remained below the light level for
recommended phototherapy.
In the entire cohort, children with bili-
rubin levels 14 mg/dL were much less
likely to receive repeat phototherapy
than those who had phototherapy
discontinued at a level >14 mg/dL. In
the 14 children who required repeat
phototherapy, 12 had phototherapy
discontinued at a level >14 mg/dL.
There were only 2 patients who
received repeat phototherapy despite
adherence to the AAP guideline of
lowering the bilirubin to 14 mg/dL.
Interestingly, one of these patients
(originally from the no-rebound group)
had a rebound bilirubin level checked
on a subsequent hospitalization, and
this rebound level still failed to prevent
a third hospitalization. He was eventu-
ally diagnosed with elliptocytosis. This
finding suggests that children who
require recurrent phototherapy despite
a level at cessation of 14 mg/dL
may warrant additional evaluation for
hemolysis.
AN OFFICIAL JOURNAL OF THE AMERICAN ACADEMY OF PEDIATRICS
Rebound Group No-Rebound Group P we found no significant differences
(n = 130) (n = 96)
5 (3.8) 4 (4.2) .98a
27.7 23.2 .001
15:19 12:54 <.001
10 (7.7) 36 (37.5) <.001
Patients in the rebound group had
longer lengths of stay and later dis-
charge times, exposing them to potential
iatrogenic complications. These patients
also received significantly less time
under phototherapy than children who
did not have a rebound level. Thus, the
rebound group spent more time in the
hospital but received less total therapy.
Keeping these patients under the lights
for additional time to lower bilirubin lev-
els to 14 mg/dL was more likely to pre-
vent readmission than monitoring them
with a rebound bilirubin level.
Furthermore, there was an increase
in cost associated with the rebound
groups prolonged length of stay and
extra laboratory testing. Our institu-
tions financial department provided
estimates for hourly hospital charges
of approximately $25.00 and $50.00
for serum bilirubin testing. Using
these estimates, the rebound bilirubin
group averaged approximately $150.00
extra per patient. This cost is further
compounded when considering the
improvements in patient flow associ-
ated with the earlier discharge times
observed in the no-rebound group.
The present studys main limitation
was its retrospective design, which
provides no concrete way to control
for why individual attending physi-
cians chose to check a rebound level
in some infants but not in others. We
tried to address this limitation by eval-
uating baseline characteristics that
typically influence this decision, and
in these characteristics between the
2 groups. There was a statistically sig-
nificant difference between bilirubin
levels at the time of phototherapy ini-
tiation and cessation, implying that the
rebound groups jaundice was more
severe than the no-rebound group.
However, the significantly shorter
period of time under phototherapy for
the rebound group argued against this
idea, as one would potentially expect
patients with more severe conditions
to require more phototherapy. In addi-
tion, the mean bilirubin levels at initia-
tion of phototherapy did not approach
exchange transfusion levels in either
group.
Another significant limitation was the
studys relatively small sample size, par-
ticularly considering that the primary
outcome of hospital readmission was
such a rare occurrence. These circum-
stances made it difficult to obtain the
power necessary to definitively detect
subtle differences in readmission rates
between the 2 groups, and our post hoc
power analysis showed our study to be
powered at 80% to detect a 12% differ-
ence in readmission rates. Before 2007,
our institutions policy was to obtain
rebound bilirubin levels on all patients
receiving phototherapy, which limited
our ability to increase patient recruit-
ment before this time period. After
2007, the hospitalist group adopted the
policy of not obtaining rebound bilirubin
levels, whereas the majority of commu-
nity pediatricians continued to obtain
rebound bilirubin levels. This clinical
environment made the comparison of
the 2 groups possible but again did not
provide a large enough sample size to
afford substantial power to detect sub-
tle differences in an outcome with such
a rare occurrence.
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 HOSPITAL Pediatrics AN OFFICIAL JOURNAL OF THE AMERICAN ACADEMY OF PEDIATRICS
CONCLUSIONS
In this retrospective study, inpatient
rebound bilirubin levels did not affect
readmission rates and were associ-
ated with an increased length of stay.
Overall, patients whose bilirubin level
was lowered to 14 mg/dL were sig-
nificantly less likely to require repeat
phototherapy. These findings provide
further evidence for initiatives aimed at
improving adherence to the AAPs rec-
ommendation to continue photother-
apy until bilirubin levels are 14 mg/dL
and to not delay hospital discharge for
monitoring of rebound bilirubin levels.
REFERENCES
1. American Academy of Pediatrics Subcom-
mittee on Hyperbilirubinemia. Management
of hyperbilirubinemia in the newborn infant
78 | VOLUME 5 ISSUE 2 www.hospitalpediatrics.org
35 or more weeks of gestation. Pediatrics.
2004;114(1):297316.
2. Yetman RJ, Parks DK, Huseby V, Mistry
K, Garcia J. Rebound bilirubin levels in
infants receiving phototherapy. J Pediatr.
1998;133(5):705707.
3. Lazar L, Litwin A, Merlob P. Phototherapy for
neonatal nonhemolytic hyperbilirubinemia.
Analysis of rebound and indications for
discontinuing therapy. Clin Pediatr (Phila).
1993;32(5):264267.
4. Maisels MJ, Kring E. Rebound in serum
bilirubin level following intensive photo-
therapy. Arch Pediatr Adolesc Med. 2002;
156(7):669672.
5. Kaplan M, Kaplan E, Hammerman C, et al.
Post-phototherapy neonatal bilirubin rebound:
a potential cause of significant hyperbilirubi-
naemia. Arch Dis Child. 2006;91(1):3134.
6. Bansal A, Jain S, Parmar VR, Chawla D.
Bilirubin rebound after intensive photo-
therapy for neonatal jaundice. Indian Pediatr.
2010;47(7):607609.
7. Tartaglia KM, Campbell J, Shaniuk P,
McClead RE. A quality project to improve
compliance with AAP guidelines for in-
patient management of neonatal hyper-
bil iru bi nemia. Hosp Pediatr. 2013;3(3):
251257.
8. Maisels MJ, Bhutani VK, Bogen D, Newman
TB, Stark AR, Watchko JF. Hyperbiliru-
binemia in the newborn infant > or
=35 weeks gestation: an update with
clarifications. Pediatrics. 2009;124(4):1193
1198.
9. Del Vecchio MT, Benstock MA, Sundel ER.
Bilirubin rebound. J Pediatr. 1999;135(4):
531532.
10. Al-Saedi SA. Rebound hyperbilirubinemia
in term infants after phototherapy. Saudi
Med J. 2002;23(11):13941397.
11. Erdeve O, Tiras U, Dallar Y. Rebound
bilirubin measurement is not required
for hyperbilirubinemia regardless of the
background attributes of newborns. J Trop
Pediatr. 2004;50(5):309.