Clofibrate for neonatal jaundice

Jaundice is a common problem in the neonatal period typically in the first week of life. It is treated quite effectively using phototherapy whereby the baby is placed under special lights for up to three to four days. Clofibrate is used in some countries in combination with phototherapy to reduce the time the baby needs to spend under lights thereby reducing parental anxiety and improved parent-baby bonding opportunities.

We have reviewed the evidence using systematic literature searches and have synthesised outcome data to see if clofibrate does has an effect on time spent under lights. We identified 12 studies and the use of clofibrate reduced time spent under lights by an average of 23 hours for both term and preterm babies.

However, most of the studies were carried out in one country, Iran, so these findings may not be generalisable to other countries.

Clofibrate has been withdrawn from the market in some countries and is no longer in use in adults (the primary indication) because of safety concerns. As such, we will no longer be updating this review.

Authors' conclusions: 

There are insufficient data from different countries on the use of clofibrate in combination with phototherapy for hyperbilirubinaemia to make recommendations for practice. Clofibrate has been withdrawn from the market in some countries and is no longer in use in adults (the primary indication) because of safety concerns. As such, we will no longer be updating this review.

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Background: 

There are many pathological conditions leading to an elevated unconjugated bilirubin level (hyperbilirubinaemia) in neonates. Currently the standard therapies for unconjugated hyperbilirubinaemia include phototherapy and exchange transfusion. In addition to phototherapy, clofibrate has been studied as a treatment for hyperbilirubinaemia in several countries.

Objectives: 

To determine the efficacy and safety of clofibrate in combination with phototherapy versus phototherapy alone in unconjugated neonatal hyperbilirubinaemia.

Search strategy: 

Randomised controlled trials were identified by searching MEDLINE (1950 to April 2012) before being translated for use in The Cochrane Library, EMBASE 1980 to April 2012 and CINAHL databases. All searches were re-run on 2 April 2012.

Selection criteria: 

We included trials where neonates with hyperbilirubinaemia received either clofibrate in combination with phototherapy or phototherapy alone or placebo in combination with phototherapy.

Data collection and analysis: 

Data were extracted and analysed independently by two review authors (MG and HM). Treatment effects on the following outcomes were determined: mean change in bilirubin levels, mean duration of treatment with phototherapy, number of exchange transfusions needed, adverse effects of clofibrate, bilirubin encephalopathy and neonatal mortality. Study authors were contacted for additional information. Studies were analysed for methodological quality in a 'Risk of bias' table.

Main results: 

Fifteen studies (two including preterm neonates and 13 including term neonates) were included in this review. All but one of the included studies were conducted in Iran. For preterm neonates, there was a significantly lower bilirubin level in the 100 mg/kg clofibrate group compared to the control group with a mean difference of -1.37 mg/dL (95% CI -2.19 mg/dL to -0.55 mg/dL) (-23 µmol/L; 95% CI -36 µmol/L to -9 µmol/L) after 48 hours. For the term neonates, there were significantly lower bilirubin levels in the clofibrate group compared to the control group after both 24 and 48 hours of treatment with a weighted mean difference of -2.14 mg/dL (95% CI -2.53 mg/dL to -1.75 mg/dL) (-37 µmol/L; 95% CI -43 µmol/L to -30 µmol/L) and -1.82 mg/dL (95% CI -2.25 mg/dL to -1.38 mg/dL) (-31 µmol/L; 95% CI -38 µmol/L to -24 µmol/L), respectively.

There was a significantly lower duration of phototherapy in the clofibrate group compared to the control group for both preterm and term neonates with a weighted mean difference of -23.82 hours (95% CI -30.46 hours to -17.18 hours) and -25.40 hours (95% CI -28.94 hours to -21.86 hours), respectively.

None of the studies reported on bilirubin encephalopathy rates, neonatal mortality rates, or the levels of parental or staff satisfactions with the interventions.