The effect of ursodeoxycholic acid on indirect hyperbilirubinemia in neonates treated with phototherapy: a randomized clinical trial

Abstract

Objectives

Indirect hyperbilirubinemia during neonatal period is a common problem, and most preterm and more than half of the term neonates find this problem. Ursodeoxycholic acid (UDCA) protects the liver against oxidative stresses and prevents cellular apoptosis. In addition, it causes stimulation of bile flow, is well tolerated by the patient, and has limited side effects. Thus, the aim of this study was to investigate the effect of UDCA in treating neonates with unconjugated hyperbilirubinemia undergoing phototherapy.

Methods

In this randomized clinical trial, 220 neonates with unconjugated hyperbilirubinemia who referred to Amir-Kabir Hospital, Arak, Iran in 2017–2018, were randomly assigned to phototherapy group (Control group) and phototherapy plus UDCA group (Intervention group) as 10 mg/kg/day. The level of total bilirubin was measured at the baseline, and after 12, and 24 h using spectrophotometric, and the duration of receiving phototherapy was also measured in both groups.

Results

The mean age of included neonates in the control and intervention group was 5.3 and 4.9 days, respectively. The results revealed that after 12 h of treatment, the total bilirubin level in the control group had diminished by 2.70 mg/dL on average while, in the intervention group, the reduction was 3.7 md/dL (p = .001) and after 24 h of treatment, the total bilirubin level in the control group had diminished by 5.22 mg/dL on average and in the intervention group, the reduction was 6.54 md/dL (p = .001). It was also observed that there is no significant difference between groups in terms of the mean of the duration required for phototherapy (p = .63).

Conclusions

UDCA combined with phototherapy enhances TSB decrease, but this effect is not relevant from a clinical point of view because it does not decrease phototherapy and hospital stay duration. Thus, this study does not support the UDCA use in the clinical practice

Trial registration

IRCT, IRCT2017071515511N2. Registered 21 Aug 2017 – Retrospectively registered, https://en.irct.ir/trial/14763.

Keywords:

• Ursodeoxycholic acid;
• indirect hyperbilirubinemia;
• neonates;
• phototherapy

Acknowledgments

The authors gratefully acknowledge the Research Council of Arak University of Medical Sciences (Grant Number: 1708) for the financial support. This work was performed in partial fulfillment of the requirements for (degree of Pediatric medicine), in School of medicine, Arak University of Medical Sciences, Arak, Iran.

Ethics approval and consent to participate

As neonates are not capable of providing ethical consent to participate, the parents or legal guardians of subjects provided written informed consent. All stages of research were conducted following the Declaration of Helsinki and the Ethical Statements of the Ethics Committee of Arak University of Medical Sciences. This study was approved by the Ethics Committee of Arak University of Medical Sciences (Ethical code: IR.ARAKMU.REC.1395.431).

Consent for publication

Not applicable.

Disclosure statement

All authors declared no conflict of interest.

Data availability statement

The datasets used and analyzed during the current study are available to be collected from the corresponding author on reasonable request.

Authors’ contributions

Study conception and design: MH, SA and RA. Data collection, statistical expertise, analysis and interpretation of data: AAH, RA, SMH and SA. Manuscript preparation, supervision, administrative support and critical revision of the paper: AAH, RA, SMH and SA. All authors read and approved the final manuscript.

Additional information

Funding

This study was financially funded by Vice-chancellor for Research of Arak University of Medical Sciences [grant number: 1708].