Objectives:

This report summarizes the evidence on the effect of bilirubin on neurodevelopmental outcomes. It also examines the role of various effect modifiers on neurodevelopment, the efficacy of phototherapy, the accuracy of transcutaneous bilirubin (TcB) measurements, and the various strategies for predicting hyperbilirubinemia.

Search strategy:

Primary research articles evaluated for this report were identified through a MEDLINE® search of English language literature published between 1966 and September 2001.

Selection criteria:

Healthy infants ≥ 34 weeks gestation or ≥ 2,500 grams with hyperbilirubinemia comprised the target population. To be included, studies reported on bilirubin level and neurodevelopmental or behavioural outcomes. For assessment of treatment efficacy, the Evidence-based Practice Center (EPC) included studies that evaluated any form of treatment for neonatal hyperbilirubinemia and had at least 10 subjects per arm. For the diagnosis review section, only studies with a minimum of 10 subjects per arm and which used laboratory assay of serum bilirubin were included.

Data collection and analysis:

The EPC reviewed 4,560 abstracts, retrieved 241 articles for close examination, and included 138 articles in this report. There were 28 articles on cases of kernicterus, 35 articles reported on correlations, 21 articles reported on treatments, and 54 articles were included in the diagnosis review section. Evidence tables of study features and results were produced. Summary tables reported an appraisal of the methodological quality of the studies and summarized results.

The EPC calculated the number needed to treat (NNT) to quantify the efficacy of treatment for neonatal hyperbilirubinemia. The EPC combined the sensitivity and specificity of the test independently and used the summary receiver operating characteristics curve to evaluate diagnostic test performance. A meta-analysis of correlation coefficients was conducted to correlate performance of TcB measurements with serum bilirubin.

Main results/conclusions:

A summary of 28 reports, which spanned over 30 years, on 123 cases of kernicterus in term or near-term infants affirms the role of elevated bilirubin level in kernicterus. The disease, although infrequent, has significant mortality (at least 10 percent) and long-term morbidity (at least 70 percent).

Except in cases of kernicterus with sequelae, use of a single total serum bilirubin (TSB) level (within the range described in the studies) to predict long-term behavioral or neurodevelopmental outcomes for infants ≥ 34 weeks gestation is inadequate and will lead to conflicting results.

Six to ten jaundiced, otherwise healthy neonates with TSB ≥ 15 mg/dl, would need to be treated with phototherapy to prevent TSB from rising above 20 mg/dl in one infant. Phototherapy combined with cessation of breastfeeding and substitution with formula was found to be the most efficient treatment protocol.

Based on the evidence from the systematic review, TcB measurements by each of the three devices described in the literature—the Minolta AirShields bilirubinometer, the Ingram Icterometer, and the SpectRx BiliCheck™—have a linear correlation to total serum bilirubin and may be useful as screening devices to detect clinically significant jaundice and decrease the need of serum bilirubin determinations.