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Rebound Hyperbilirubinemia
Following Inpatient Phototherapy
Pearl W. Chang, MD,a Michael W. Kuzniewicz, MD, MPH,b,c Charles E. McCulloch, PhD,d Thomas B. Newman, MD, MPHb,c,d
OBJECTIVES: The American Academy of Pediatrics provides little guidance on when to abstract
discontinue phototherapy in newborns treated for hyperbilirubinemia. We sought to
develop a prediction rule to estimate the probability of rebound hyperbilirubinemia after
inpatient phototherapy.
METHODS: Subjects for this retrospective cohort study were infants born in 2012 to 2014 at
≥35 weeks’ gestation at 16 Kaiser Permanente Northern California hospitals who received
inpatient phototherapy before age 14 days. We defined rebound as the return of total serum
bilirubin (TSB) to phototherapy threshold within 72 hours of phototherapy termination. We
used stepwise logistic regression to select predictors of rebound hyperbilirubinemia and
devised and validated a prediction score by using split sample validation.
RESULTS: Of the 7048 infants treated with inpatient phototherapy, 4.6% had rebound
hyperbilirubinemia. Our prediction score consisted of 3 variables: gestational age <38
weeks (adjusted odds ratio [aOR] 4.7; 95% confidence interval [CI], 3.0–7.3), younger age
at phototherapy initiation (aOR 0.51 per day; 95% CI, 0.38–0.68), and TSB relative to the
treatment threshold at phototherapy termination (aOR 1.5 per mg/dL; 95% CI, 1.4–1.7).
The model performed well with an area under the receiver operating characteristic curve
of 0.89 (95% CI, 0.86–0.91) in the derivation data set and 0.88 (95% CI, 0.86–0.90) in the
validation data set. Approximately 70% of infants had scores <20, which correspond to a
<4% probability of rebound hyperbilirubinemia.
CONCLUSIONS: The risk of rebound hyperbilirubinemia can be quantified according to an
infant’s gestational age, age at phototherapy initiation, and TSB relative to the treatment
threshold at phototherapy termination.
aDepartment
WHAT’S KNOWN ON THIS SUBJECT: There are no
of Pediatrics, Seattle Children’s Hospital, Seattle, Washington; bDivision of Research, Kaiser
Permanente Northern California, Oakland, California; and Departments of cPediatrics, and dEpidemiology & standards and little evidence to support decisions
Biostatistics, University of California, San Francisco, California about when to discontinue phototherapy in
newborns being treated for hyperbilirubinemia.
Dr Chang conceptualized and designed the study, carried out statistical analysis and
interpretation of data, and drafted the initial manuscript; Drs Kuzniewicz and McCulloch assisted WHAT THIS STUDY ADDS: We describe a model to
with study design; Dr Newman conceptualized and designed the study, obtained funding, and quantify the risk of rebound hyperbilirubinemia.
guided statistical analysis and interpretation of data; and all authors revised and reviewed the This model will enable clinicians to discontinue
manuscript and approved the final manuscript as submitted. phototherapy when the risk of rebound
DOI: 10.1542/peds.2016-2896 hyperbilirubinemia reaches a suitably low level.
Accepted for publication Dec 19, 2016
Address correspondence to Pearl W. Chang, MD, Seattle Children’s Hospital, M/S FA.2.115, PO Box
5371, Seattle, WA 98145-5005. E-mail: pearlchangmd@gmail.com To cite: Chang PW, Kuzniewicz MW, McCulloch CE, et al. A
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Clinical Prediction Rule for Rebound Hyperbilirubinemia
Following Inpatient Phototherapy. Pediatrics. 2017;139(3):
Copyright © 2017 by the American Academy of Pediatrics e20162896
FIGURE 2
Probability of rebound hyperbilirubinemia by score. Score = 15 (if gestational age <38 weeks) − 7 × (age in days at phototherapy initiation) − 4 × (AAP
phototherapy threshold − TSB at phototherapy termination) + 50.
TSB of 5 mg/dL below treatment for whom follow-up TSB testing This study has limitations. One of our
threshold gives a score of 17 is difficult or readmission for key predictor variables, the TSB at
and an estimated 2.8% probability hyperbilirubinemia presents time of phototherapy termination,
of rebound hyperbilirubinemia. a greater hardship, it may make was estimated by extrapolation
In comparison, the probability sense to continue phototherapy for the majority of our subjects,
of rebound would increase to 6.0% longer. On the other hand, a 10% which presumably worsened the
at a TSB of 3 mg/dL below and or 15% risk may be acceptable for discrimination of the prediction rule.
12.3% at a TSB of 1 mg/dL below a reliable family close to an infant However, we envision clinicians
treatment threshold. In infants care center. using the rule to decide whether to
Additionally, we based our variable externally validate our prediction about when to discontinue
for home phototherapy on equipment rule, a consideration for future phototherapy.
orders, and therefore we did not research.
know precisely whether and when ACKNOWLEDGMENT
home phototherapy was used. There The authors thank Dr Andrea C.
may have been infants whose TSB Wickremasinghe for her critical review
returned to treatment threshold CONCLUSIONS
of the manuscript and invaluable
within 72 hours who did not have Rebound hyperbilirubinemia revisions and suggestions.
a TSB measurement until later. can be predicted with
Given this limitation and the use excellent discrimination by an ABBREVIATIONS
of home phototherapy, the risk of infant’s gestational age, age at
AAP: American Academy of
rebound hyperbilirubinemia may be initiation of phototherapy, and
Pediatrics
underestimated in our study, which relative TSB at phototherapy
aOR: adjusted odds ratio
may not be generalizable to infants termination. With a prediction
AUROC: area under the receiver
for whom home phototherapy is not score of <20, phototherapy
operating characteristic
an option. We also only examined can be discontinued with <4%
curve
rebound hyperbilirubinemia after probability of rebound. Clinical
CI: confidence interval
infants’ first inpatient phototherapy, implementation of this prediction
DAT: direct antiglobulin test
and rebound risks may be different rule via a Web-based calculator or
OR: odds ratio
after subsequent phototherapy. integration into electronic medical
TSB: total serum bilirubin
Finally, we were not able to records could help guide decisions
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
FUNDING: Partially supported by grant R01HS020618 from the Agency for Healthcare Research and Quality. The content is solely the responsibility of the authors
and does not necessarily represent the official views of the Agency for Healthcare Research and Quality. The funder played no role in the design and conduct of
the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
COMPANION PAPER: A companion to this article can be found online at www.pediatrics.org/cgi/doi/10.1542/peds.2016-3832.
REFERENCES
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References This article cites 15 articles, 5 of which you can access for free at:
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