Effect of Oral Zinc Supplementation on Serum Bilirubin Reduction in Hospitalized Neonates with Jaundice in Mofid and Mahdieh Hospitals: A Randomized Double-Blind Clinical Trial

Effect of oral zinc supplementation on reducing serum bilirubin levels in neonates with hyperbilirubinemia admitted to Mofid and Mahdieh Children’s Hospitals.

This study will be conducted as a randomized controlled clinical trial, with a double-blind, placebo-controlled, parallel-group design. This phase III trial will be performed on 100 term and near-term neonates with indirect neonatal hyperbilirubinemia.

The study will be conducted in the neonatal units of Mofid and Mahdieh Children’s Hospitals. Neonates will be randomly allocated to intervention and control groups. The intervention group will receive standard care plus oral zinc (10 mg/day), while the control group will receive standard care plus a placebo. Total serum bilirubin (TSB) will be measured at baseline and at 6, 12, 24, 48, 72, and 96 hours after intervention in both groups.

Term and near-term neonates (gestational age ≥35 weeks) hospitalized with indirect hyperbilirubinemia requiring phototherapy, adequate oral feeding tolerance, and written parental consent were included in the study. Neonates with early-onset jaundice (<24 hours), sepsis, need for mechanical ventilation, major congenital anomalies, gastrointestinal disorders, requirement for exchange transfusion, or evidence of hemolysis were excluded.

Neonates in the intervention group will receive standard care plus oral zinc (10 mg/day), while the control group will receive standard care plus a matched placebo. Standard treatment includes phototherapy, adequate feeding, and routine clinical and vital sign monitoring, with identical phototherapy devices and standardized settings in both groups.

Total serum bilirubin (TSB) level at 48 hours after initiation of the intervention.

To ensure balanced group sizes throughout the enrollment process, block randomization with a fixed block size of four will be used. Neonates will be randomized in blocks of four. Randomization will be stratified by sex and baseline total serum bilirubin level (<18 mg/dL and ≥18 mg/dL) to ensure a balanced distribution of the initial severity of hyperbilirubinemia between the intervention and control groups. The random allocation sequence will be generated by an independent individual who is not involved in the study using Random Allocation Software. Allocation assignments will be placed in sequentially numbered, opaque, sealed envelopes to ensure allocation concealment. Upon enrollment of each eligible neonate, the next envelope in the predetermined sequence will be opened, and only the designated pharmacist responsible for preparing the study intervention will be informed of the treatment assignment. The individual responsible for generating the randomization sequence and maintaining the allocation envelopes will have no involvement in participant recruitment, clinical management, outcome assessment, data collection, or statistical analysis.

This study will be conducted as a double-blind clinical trial. The parents or legal guardians of the neonates, as well as all members of the research team, including the treating physicians, ward nurses, the researcher responsible for data collection, the outcome assessor, and the statistician, will remain blinded to group allocation throughout the study. Only the designated pharmacist responsible for preparing the study intervention will be aware of the allocation codes. The allocation codes will remain concealed until completion of the final statistical analysis, unless emergency unblinding is required due to a serious adverse event or when knowledge of the treatment assignment is deemed necessary for appropriate clinical management.

All data collected during the study will be de-identified and made available for data sharing.

The de-identified study data will be available for sharing upon submission of the manuscript derived from this study to a peer-reviewed journal.

Access to the de-identified study data will be available to all interested readers.

The complete de-identified dataset may be used for pooled analyses or meta-analyses upon reasonable request to the corresponding author and with the necessary approval.

Vahide Zeinali, email: v.zeinali4183@sbmu.ac.ir

Upon publication of the study, a public electronic link to the de-identified dataset will be provided. During the publication process (before online publication), researchers may request access to the data by contacting the corresponding author via email and providing the purpose and details of their request. Subject to approval by the research team, the requested data will be shared within 24 hours.