Effect of clofibrate in jaundiced term neonates
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《美国医学杂志》
Department of Pediatrics, Advanced Pediatrics Center, Post Graduate Institute of Medical Education and Research, Chandigarh, India
We have read with interest the trial by Mohammadzadeh et al[1] who reported the use of single dose of clofibrate in jaundiced term babies. Indeed, in developing countries such a simple pharmacological intervention would reduce treatment costs and hospital stays due to jaundice.
Before the results of the study are accepted and implemented for daily practice, certain factors which could have brought in an element of bias as a consequence of lack of placebo group must be resolved. The mean age of enrolment was 8-9 days, the time when in most of the term babies with hyperbilirubinemia, the bilirubin level will be on receding trend. Segregation of results for infants who could be enroled before day 5 would be more meaningful. Irradiance of the phototherapy should have been measured and demonstrated to be equal since this was an important additional intervention.
As there was no placebo administered to the control group, there is a possibility of bias in the form of the treatment group being given the better form of phototherapy (blue vs white phototherapy or newer units vs older ones) and other co-interventions like better hydration etc.
The authors have chosen to use 100 mg/kg dose of clofibrate. Safety of such a large dose is not clear in neonates. Bourget et al[2] have shown that with 100 mg/kg dose the plasma half life of clofibric acid can reach up to more than 100 hours, and with the use of clofibrate as less as 6 days in adults with impaired renal failure, acute muscular syndrome with microscopically demonstrated muscular atropy has been described.[3] It would have been worthwhile measuring the amount of clofibric acid in these babies and level of muscle enzymes over at least a period of 7 days.
Finally, clofibrate has been shown to be carcinogenic in animal and humans.[4] Long term follow-up of babies treated with single dose of clofibrate should be available before this therapy can be recommended for widespread use.
References
1. Mohammadzadeh A, Farhat AS, Iranpour R. Effect of clofibrate in jaundiced term newborns. Indian J Pediatr 2005; 72 (2) : 123-126.
2. Bourget P, Broise I, Quinquis-Desmaris V, Gabilan JC. Pharmacokinetics of clofibrate in jaundiced newborn infants at term. Arch Pediatr 1995; 2(8) : 722-728.
3. Rimon D, Ludatscher R, Cohen L. Clofibrate-induced muscular syndrome. Case report with ultrastructural findings and review of the literature. Isr J Med Sci 1984; 20(11) : 1082-1086.
4. Rao MS, Reddy, JK. Hepatocarcinogenesis of peroxisome proliferators. Ann NY Acad Sci 1996; 804 : 573-587.(Wazir S, Angiti RR, Kumar)
We have read with interest the trial by Mohammadzadeh et al[1] who reported the use of single dose of clofibrate in jaundiced term babies. Indeed, in developing countries such a simple pharmacological intervention would reduce treatment costs and hospital stays due to jaundice.
Before the results of the study are accepted and implemented for daily practice, certain factors which could have brought in an element of bias as a consequence of lack of placebo group must be resolved. The mean age of enrolment was 8-9 days, the time when in most of the term babies with hyperbilirubinemia, the bilirubin level will be on receding trend. Segregation of results for infants who could be enroled before day 5 would be more meaningful. Irradiance of the phototherapy should have been measured and demonstrated to be equal since this was an important additional intervention.
As there was no placebo administered to the control group, there is a possibility of bias in the form of the treatment group being given the better form of phototherapy (blue vs white phototherapy or newer units vs older ones) and other co-interventions like better hydration etc.
The authors have chosen to use 100 mg/kg dose of clofibrate. Safety of such a large dose is not clear in neonates. Bourget et al[2] have shown that with 100 mg/kg dose the plasma half life of clofibric acid can reach up to more than 100 hours, and with the use of clofibrate as less as 6 days in adults with impaired renal failure, acute muscular syndrome with microscopically demonstrated muscular atropy has been described.[3] It would have been worthwhile measuring the amount of clofibric acid in these babies and level of muscle enzymes over at least a period of 7 days.
Finally, clofibrate has been shown to be carcinogenic in animal and humans.[4] Long term follow-up of babies treated with single dose of clofibrate should be available before this therapy can be recommended for widespread use.
References
1. Mohammadzadeh A, Farhat AS, Iranpour R. Effect of clofibrate in jaundiced term newborns. Indian J Pediatr 2005; 72 (2) : 123-126.
2. Bourget P, Broise I, Quinquis-Desmaris V, Gabilan JC. Pharmacokinetics of clofibrate in jaundiced newborn infants at term. Arch Pediatr 1995; 2(8) : 722-728.
3. Rimon D, Ludatscher R, Cohen L. Clofibrate-induced muscular syndrome. Case report with ultrastructural findings and review of the literature. Isr J Med Sci 1984; 20(11) : 1082-1086.
4. Rao MS, Reddy, JK. Hepatocarcinogenesis of peroxisome proliferators. Ann NY Acad Sci 1996; 804 : 573-587.(Wazir S, Angiti RR, Kumar)