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Rebound in Serum Bilirubin Level Following Intensive Phototherapy
M. Jeffrey Maisels, MB, BCh;
Elizabeth Kring, RN
Arch Pediatr Adolesc Med. 2002;156:669-672.
ABSTRACT
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Objectives To document the need for repeated phototherapy (as an index of significant
rebound in serum bilirubin levels) following the discontinuation of intensive
phototherapy and to compare the use of repeated phototherapy in infants who
first received phototherapy during their birth hospitalization with the use
of first-time phototherapy on readmission after infants were discharged from
their birth hospitalization.
Design A retrospective review of the medical records of 303 term and near-term
newborns treated between January 1996 and December 1998, who received phototherapy
in our well-baby nursery during their birth hospitalization (group 1, n =
158) or who had been discharged from the nursery and were readmitted for phototherapy
(group 2, n = 144). All infants received intensive phototherapy but were managed
by individual attending pediatricians. Rebound measurements were included
if a bilirubin level was obtained between 4 and 48 hours after discontinuing
phototherapy.
Setting Newborn nursery and pediatric ward of a large community hospital.
Main Outcome Measures The number of infants who received repeated phototherapy and the magnitude
of the bilirubin-level rebound.
Results Thirteen (8.2%) of 158 (95% confidence interval [CI], 3.9-12.4) infants
treated with phototherapy before discharge from the nursery (group 1) and
only 1 (0.7%) of 144 (95% CI, 0-2.0) infants who first received phototherapy
on readmission (group 2) received repeated phototherapy (P = .002). Phototherapy was discontinued when mean ± SD total
serum bilirubin levels were, 10.4 ± 1.8 mg/dL (178 ± 31 µmol/L)
in group 1 and 12.3 ± 1.3 mg/dL (210 ± 22 µmol/L) in group
2. The mean ± SD increase in the total serum bilirubin levels following
rebound was 1.3 ± 2.0 mg/dL (22 ± 34 µmol/L) in group
1 and 0.27 ± 1.46 mg/dL (4.6 ± 25 µmol/L) in group 2 (P<.001).
Conclusions It is not necessary to keep infants in the hospital to check for rebound.
However, for infants who require phototherapy during their birth hospitalization
and for those with significant hemolytic disease, we recommend obtaining a
follow-up bilirubin level 24 hours after discharge. This is probably not necessary
in those who are readmitted for phototherapy but, because rare instances of
significant rebound have occurred in these infants, additional clinical follow-up
is appropriate, particularly if phototherapy is discontinued at higher total
serum bilirubin levels than used in this study.
INTRODUCTION
DECREASING hospital length of stay is an objective sought by physicians
and administrators alike, and the American Academy of Pediatrics has recommended
that infants need not be kept in the hospital to measure rebound bilirubin
levels following the discontinuation of phototherapy.1
Nevertheless, many physicians keep infants in the hospital for several hours
to obtain a rebound bilirubin level after phototherapy has been discontinued.
Only 2 observational studies have specifically addressed this issue.2-3 These studies included both term and
preterm infants and concluded that the measurement of rebound bilirubin levels
following phototherapy was probably unnecessary. Examination of other published
data suggests that significant rebound following discontinuation of phototherapy
is rare.4-5 The infants in all
of these studies were treated during their birth hospitalization (as opposed
to having been readmitted for phototherapy). Infants who are discharged following
birth and readmitted with hyperbilirubinemia have significantly higher total
serum bilirubin (TSB) levels than those who are treated before they are discharged
from the nursery.
Since 1995, we have used intensive phototherapy6
to treat all infants with hyperbilirubinemia who require phototherapy. Since
this type of phototherapy produces a more rapid decline in the TSB level than
does conventional phototherapy, it is possible that a greater rebound might
occur. Our objective was to document the incidence of rebound of TSB levels
after termination of phototherapy and to compare the rebound in a group of
infants who received phototherapy during their birth hospitalization with
those treated after discharge and readmission to the hospital.
SUBJECTS AND METHODS
We reviewed the medical records of 2 groups of infants treated between
January 1996 and December 1998. Group 1 consisted of 158 term and near-term
(gestational age, 33-37 weeks) newborns who received phototherapy in our well-baby
nursery during their birth hospitalization. Infants who received phototherapy
in the special-care or intensive-care nurseries were excluded. Group 2 consisted
of 144 infants who had been discharged from the well-baby nursery and had
not received phototherapy during their initial hospital stay but were subsequently
readmitted for phototherapy. All infants were treated in bassinets, not incubators,
and phototherapy was administered with 8 special blue fluorescent tubes (F20T12/BB;
General Electric, Milwaukee, Wis) placed 10 cm above the infant. This produced
an average irradiance of 43 µW/cm2 per nanometer, at 425
to 475 nm, measured at the surface of the infant with an Olympic Bilimeter
Mark II (Olympic Medical Corp, Seattle, Wash). In addition, all infants lay
on a fiberoptic blanket (Ohmeda Biliblanket; Ohmada Inc, Columbia, Md, or
Fiberoptic Medical Wallaby; Fiberoptic Medical Products Inc, Allentown, Pa)
and the mean irradiance of the blanket was 18 to 21 µW/cm2
per nanometer.
The decisions to initiate and discontinue phototherapy and to obtain
a rebound TSB level were made by the responsible attending pediatrician. Of
those infants readmitted for phototherapy, 64 (44.4%) of 144 had been born
at other hospitals. The data extracted from the medical records included the
gestational age, type of feeding, age, and TSB level at initiation of phototherapy
and at termination of phototherapy, duration of phototherapy, rebound TSB
level measurement, maternal and infant blood types, and direct Coombs test
result when available. Rebound measurements were included if a TSB level was
obtained between 4 and 48 hours after discontinuing phototherapy. We compared
continuous data using the 2-sample t test (unless
otherwise indicated) and categorical data using the Fisher exact test. Unless
otherwise indicated, data are expressed as mean ± SD. The study was
approved by the hospital human investigation committee.
RESULTS
The clinical data and results are presented in Table 1. One hundred nineteen (75.3%) of 158 infants in group 1
and 115 (79%) of 144 infants in group 2 had rebound TSB levels measured at
17.6 ± 11 (range, 4-48) hours and 16.5 ± 10.5 (range, 4-43)
hours, respectively, following the termination of phototherapy. The mean increase
in TSB level following rebound was 1.3 ± 2.0 mg/dL (22 ± 34
µmol/L) in group 1 and 0.27 ± 1.46 mg/dL (4.6 ± 25 µmol/L)
in group 2 (P<.001). In group 1, phototherapy
was initiated at 47.5 ± 22.3 (range, 1-106) hours. In this group, 13
(8.2%) of 158 infants (95% confidence interval [CI], 3.9-12.4) received repeated
phototherapy, which was initiated at a mean age of 107.3 + 41.4 hours and
at a mean TSB level of 17.2 ± 3.9 mg/dL (294 ± 67 µmol/L).
Five were exclusively breastfed and 8 received breast milk and formula. Eight
of these 13 mothers had type O blood and direct Coombs tests were performed
in 7 infants. Only 2 of these infants had a positive Coombs test result (1
ABO incompatibility, 1 anti C) and 6 had bruising. No cause for the hyperbilirubinemia
was found in the remaining 5. Six infants received repeated phototherapy before
discharge and 7 were discharged and readmitted 24 to 124 hours later. There
were no differences between the infants in group 1 who did or did not receive
repeated phototherapy except that all 13 infants who received repeated phototherapy
were fully or partially breastfed vs 51.0% of those who did not receive repeated
phototherapy (P<.001). In 3 infants who received
a repeated course of phototherapy while still in the nursery, the TSB level
before the repeated course was lower than the level at which phototherapy
had been started originally, calling into question the need for repeated phototherapy.
In group 2, phototherapy was initiated at a mean age of 4.6 ±
1.8 days. (Because 44% of these infants were born at other hospitals, the
exact time of birth was not available from the hospital record and thus precluded
precise calculation of the age in hours.) Only 1 (0.7%) of 144 infants (95%
CI, 0-2.0) in this group received repeated phototherapy. This 5436-g male
had O Rh-positive blood type, was formula-fed, and his TSB level on admission
on day 4 was 23.1 mg/dL (395 µmol/L). His TSB level decreased to 13.2
mg/dL (226 µmol/L) after 31 hours of phototherapy (a decrease of 0.32
mg/dL [5.5 µmol/L] per hour). Nine hours after stopping phototherapy,
his TSB level was 17.4 mg/dL (298 µmol/L) and phototherapy was reinstituted.
COMMENT
Two observational studies have specifically addressed the question of
rebound,2-3 but data on rebound
of TSB level are provided in other studies.4-5
The infants in all of these studies were treated during their birth hospitalization
only; ours is the first, to our knowledge, to examine TSB level rebound in
a population readmitted for phototherapy and to compare these infants with
those treated during their birth hospitalization. Our data confirm the previous
observations dealing with TSB level rebound after phototherapy. In the study
by Lazar et al,2 none of 58 infants weighing
more than 1500 g had a TSB level rebound that required additional phototherapy.
Yetman et al3 studied 264 infants, all of whom
were treated during their birth hospitalization. Repeated phototherapy was
required in 11 infants but 9 of these infants weighed less than 1800 g. In
the other 2 infants, the authors considered the reinstitution of phototherapy
to be unnecessary. Tan et al5 studied 3802
infants who received phototherapy for nonhemolytic jaundice. Of 2879 full-term
infants receiving standard white light phototherapy, only 24 (0.66%) required
a second dose of phototherapy following rebound compared with 4 (2.8%) of
141 term infants receiving intensive phototherapy with special blue lights
(P<.001).
In the 1974-1976 collaborative phototherapy study of the National Institutes
of Child Health and Human Development (Bethesda, Md), 672 infants received
phototherapy.4 Those with birth weights less
than 2000 g were treated "prophylactically" starting at age 24 ± 12
hours. The authors report a rebound in serum TSB level "usually less than
1.0 mg/dL" that occurred within 24 hours after discontinuing phototherapy.
Seventy infants with birth weights of 2000 to 2499 g in this study were treated
with phototherapy when their TSB values reached 10 mg/dL (171 µmol/L),
and 140 infants with birth weights greater than or equal to 2500 g received
phototherapy at a mean TSB level of 15.7 ± 2.5 mg/dL (269 ±
43 µmol/L) at age 62.5 hours. In both groups of infants, mean TSB levels
continued to decline once phototherapy was discontinued.
Our data and the data from these studies show that it is unnecessary
to keep an infant in the hospital after phototherapy has been discontinued
to check for a rebound of the TSB level. This applies to infants with Coombs-positive
ABO incompatibility as well. Yetman et al2
found no rebound in any of 57 infants who had positive direct Coombs test
results and received phototherapy. An important difference between our study
and that of Yetman et al3 is that our infants
received phototherapy for an average of only 25.8 hours (and some as little
as 5 hours), while the average duration of phototherapy in their study was
121 hours.
The differences in the apparent cause of hyperbilirubinemia between
the 2 groups of infants are instructive. ABO incompatibility with a positive
direct Coombs test result occurred in 22% of infants (in whom blood type and
Coombs test results were obtained) in group 1 but only 3.5% of those in group
2. Even in the absence of blood group incompatibility, there is evidence that
increased bilirubin production (including bruising) is the most likely cause
of early hyperbilirubinemia and rebound in the infants in group 1.7 We measured end-tidal carbon monoxide concentrations,
corrected for ambient carbon monoxide (an index of heme catabolism and bilirubin
production)8 in infants in our nursery who
developed significant jaundice (TSB >75th percentile for age in hours).7 In 89%, the end-tidal carbon monoxide concentration
corrected for ambient carbon monoxide was above the 50th percentile and in
55% it was above the 75th percentile compared with controls. This suggests
that most infants who develop early jaundice have an increase in their rate
of bilirubin production.7 On the other hand
(and not surprisingly), breastfeeding seemed to play a much more significant
role in those infants readmitted for hyperbilirubinemia than in those who
developed early hyperbilirubinemia.
The differences between groups 1 and 2 probably reflect both the causes
of hyperbilirubinemia and the natural history of neonatal jaundice. As discussed,
far fewer infants in group 2 (than in group 1) had evidence of hemolysis.
Furthermore, in group 2, because phototherapy was started at an average age
of 4.6 ± 1.8 days, it is likely that the TSB level was approaching,
or had reached its peak, so that rebound was much less likely. The above reasons
also account, in part, for the differences in the efficacy of phototherapy
in the 2 groups. In group 1, phototherapy produced a much slower decline in
TSB levels (0.11 ± 0.1 mg/dL [1.9 ± 1.7 µmol/L] per hour)
than in group 2 (0.3 ± 0.13 mg/dL [5.1 ± 2.2 µmol/L] per
hour) (P<.001). Perhaps the most important reason
for this, however, is the difference in the mean TSB level at the start of
phototherapy: 12.7 mg/dL (217 µmol/L) in group 1 vs 20.1 mg/dL (344
µmol/L) in group 2. It is well known that the higher the initial TSB
level, the better the response to phototherapy.9
Weaknesses in this study include its design (a retrospective survey)
and the fact that decisions to measure rebound TSB levels or to initiate or
restart phototherapy were not established prior to the study and were made
by individual attending pediatricians. Thus, the need for repeated phototherapy
in some infants could be questioned. On the other hand, follow-up was inconsistent,
so we do not know if significant rebound was missed in some infants who might
have required additional phototherapy. Nevertheless, when measured, the rebound
in both groups was small. This confirms our conclusion that infants need not
remain in the hospital to have rebound TSB levels measured. Clinical follow-up
and/or an outpatient TSB level should identify infants who need additional
treatment.
| What This Study Adds
Many physicians keep infants hospitalized for measurement of rebound
TSB levels following the discontinuation of phototherapy, even though published
data have suggested that this is not necessary. The studies to date have been
limited to infants who received phototherapy during the birth hospitalization
and there are very limited data on infants who have received intensive (vs
standard) phototherapy. To our knowledge, this study is the first to provide
data on the rebound of TSB levels that occurs in infants who have been discharged
following birth and then readmitted for intensive phototherapy and the first
to compare infants who are treated during their birth hospitalization with
those treated after discharge and readmission to the hospital. We provide
guidelines for the physician regarding the follow-up of infants after phototherapy
is discontinued.
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AUTHOR INFORMATION
Accepted for publication April 3, 2002.
Corresponding author and reprints: M. Jeffrey Maisels, MB, BCh, Department
of Pediatrics, William Beaumont Hospital, 3601 W 13 Mile Rd, Royal Oak, MI
48073 (e-mail: jmaisels{at}beaumont.edu).
From the Department of Pediatrics, William Beaumont Hospital, Royal
Oak, Mich.
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