U.S. flag

An official website of the United States government

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Cover of Screening for Bilirubin Encephalopathy

Screening for Bilirubin Encephalopathy

Evidence Syntheses, No. 72

Investigators: , MD, , MPH, , MD, MPH, , MLitt, and , MD.

Author Information and Affiliations
Rockville (MD): Agency for Healthcare Research and Quality (US); .
Report No.: 10-05140-EF-1

Structured Abstract


Kernicterus or chronic bilirubin encephalopathy is a devastating disease. Thus, it is important to examine strategies to prevent the development of kernicterus.


To systematically review evidence for the effectiveness of strategies to prevent chronic bilirubin encephalopathy. This is an update of our previous evidence report.

Data Sources:

We searched Medline for articles from September, 2001 to August, 2007 using the MeSH terms and keywords, such as “jaundice,” “bilirubin,” “hyperbilirubinemia,” and “kernicterus.” For additional studies, we examined the bibliographies in existing studies and also consulted the lead experts from USPSTF.

Study Selection:

We identified 18 articles that met our inclusion/exclusion criteria. Three studies in two publications addressed key question 2 (Does risk factor assessment accurately identify infants who may benefit from bilirubin testing?), nine studies addressed key question 3 (Does bilirubin testing accurately identify infants who may benefit from phototherapy?), and nine studies addressed key question 6 (What are the harms of treatment with phototherapy?). Of the 11 studies that addressed key questions 2 and 3, five were of fair quality; six were of poor quality according to US Preventive Services Task Force (USPSTF) criteria. We did not grade the methodological quality for the nine studies that addressed key question 6.

Data Extraction:

Data elements were abstracted on to standardized forms and included information about the study setting, population, control, description of screening strategy, definitions of bilirubin encephalopathy and elevated bilirubin, and methods of analyses. Any adverse events or other effects from screening or phototherapy were also extracted. We also assessed the internal validity of the studies according to USPSTF criteria.

Data Synthesis (Results):

There was no study that directly addressed the effectiveness of using risk factor assessment and/or bilirubin testing to reduce the incidence of kernicterus. Three fair quality studies (two nested case-control studies and a large retrospective cohort) examined the effectiveness of either using a risk score or a risk index to predict significant hyperbilirubinemia. The data suggest comparable predictability of the risk score (newborn and familial jaundice history and clinical characteristics) and the modified risk index (i.e., the risk score without family history of jaundice in a newborn) in predicting later significant hyperbilirubinemia. Three fair quality studies (one prospective and two retrospective cohorts) and one poor quality prospective study suggest comparable diagnostic abilities of early total serum bilirubin (TSB) measurements to predict late high TSB measurements. Results from one fair quality retrospective study comparing the ability of various screening strategies in predicting later hyperbilirubinemia suggest that the combination of using the modified risk index with early TSB levels significantly enhanced prediction than using either one of the strategies alone. None of the studies in this review assessed potential harms of screening. Studies in this review did not evaluate the effectiveness of phototherapy in reducing the risk of bilirubin encephalopathy. Our previous review reported that one needs to treat six to ten otherwise healthy jaundiced neonates with TSB ≥ 15 mg/dL by phototherapy in order to prevent the TSB in one infant from rising above 20 mg/dL. No definitive harm could be attributed to phototherapy. One retrospective study found an association in children between sizes of melanocytic nevi and exposure to neonatal phototherapy.


A study that directly evaluates the effectiveness of different strategies to reduce the incidence of kernicterus is not feasible given the rare occurrence of kernicterus. For practical consideration, studies on the effectiveness of different strategies to reduce the incidence of bilirubin encephalopathy could only rely on a surrogate outcome like serum bilirubin level. Based on retrospective analyses among infants who had both early and late TSB measurements available, the combination of risk factors and early TSB measurement has better diagnostic ability to predict clinically significant hyperbilirubinemia compared to risk factors alone.


This report is based on research conducted by the Tufts-New England Medical Center Evidence-based Practice Center (EPC)1 under contract to the Agency for Healthcare Research and Quality (AHRQ)2 (Contract No. 290-02-0022).

Suggested citation:

Ip S, Chung M, Trikalinos T, DeVine D, Lau J. Screening for Bilirubin Encephalopathy. Evidence Synthesis No. 72. AHRQ Publication No. 10-05140-EF-1. Rockville, Maryland: Agency for Healthcare Research and Quality, October 2009.

The investigators involved have declared no conflicts of interest with objectively conducting this research. The findings and conclusions in this document are those of the authors, who are responsible for its content, and do not necessarily represent the views of AHRQ. No statement in this report should be construed as an official position of AHRQ or of the US Department of Health and Human Services.

The information in this report is intended to help clinicians, employers, policymakers, and others make informed decisions about the provision of health care services. This report is intended as a reference and not as a substitute for clinical judgment.

This report may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or US Department of Health and Human Services endorsement of such derivative products may not be stated or implied.


Tufts-New England Medical Center, 800 Washington Street, Box 63, Boston, Massachusetts 02111.


540 Gaither Road, Rockville, MD 20850. www‚Äč.ahrq.gov

Bookshelf ID: NBK34036PMID: 20722171


Related information

Similar articles in PubMed

See reviews...See all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...