Efficacy of oral zinc in neonatal jaundice admitted for phototherapy: A Randomized Controlled Trial

INTRODUCTION:

Neonatal jaundice is one of the commonest causes for admission in NICU during the initial month of life. As per NNPD the incidence of jaundice in in-house live-births is 3.3% and extramural admissions are 22.1%. The mainstay of treatment for neonatal jaundice is phototherapy and exchange transfusion. Other treatment modalities include the use of intravenous immunoglobulin, metalloporphyrins and Phenobarbital. Oral zinc salts will adsorb the unconjugated bilirubin from the micelle formed by the bile salts. This will reduce the enterohepatic circulation and helps in excretion by stool thereby decrease the serum bilirubin. There are some studies which suggest that both maternal and neonatal serum zinc deficiency is associated with neonatal jaundice requiring phototherapy. Except promising results in Gilbert syndrome with zinc supplementation, all other studies in term and preterm neonates are inconclusive. Therefore the present study aims to evaluate the efficacy and dosage of oral zinc in reducing serum bilirubin levels in neonates with gestational age (GA) of ≥35 weeks admitted for phototherapy.

AIMS AND OBJECTIVES:

Hypothesis-Oral zinc salt supplementation will reduce the unconjugated serum bilirubin and duration of phototherapy in neonates.

Primary objective- To evaluate the efficacy of oral zinc for reduction of serum bilirubin at 12, 24 and 48hrs of initiation of phototherapy.

Secondary objectives**-**

1) Reduction in duration of phototherapy and length of hospital stay.

2. Adverse events associated with zinc supplementation.

3. Estimation of serum zinc levels at pre and post-phototherapy time points.

MATERIALS AND METHODOLOGY:

PLACE OF STUDY: Kalinga institute of Medical sciences, Bhubaneswar

STUDY DURATION: From FEB 2024 to JULY 2026

STUDY DESIGN: Interventional study - Randomised, Double     blinded, parallel Trial.

Patients will be of allocated -computer generated random list.

Allocation concealment- opaque sealed envelope.

STUDY POPULATION:  Neonates (GA ≥35 weeks) admitted in the NICU for phototherapy will be enrolled in the study after taking informed consent from parents.

Sample size: Assuming an effect size 0.3,5% level of significance and 80% power, the calculated sample size for 3 groups comparison on continuous  primary outcome measure is 111(i.e., 37 in each group )

No of Cases (expected/calculated): 37 in each intervention group (total-74)

No of Controls: 37

Inclusion criteria**-** Neonates (GA ≥35 weeks) admitted in NICU for phototherapy as per UK-NICE guideline.

Exclusion criteria**-**

1)   Severe hyperbilirubinemia( need of escalation therapy and exchange transfusion)

2)   Major congenital abnormality

3)   Sick neonate (sepsis, birth asphyxia, feed intolerance, mechanical ventilation, IEM) where oral feeding contraindicated.

4)   Rebound hyperbilirubinemia who require phototherapy again

5)   Maternal Phenobarbital intake.

Arm of the trial**-**

Intervention arm-1 will receive zinc salt (@ oral 5mg/day)

Intervention arm-2 will receive zinc salt (@ oral 10mg/day)

Control arm will receive placebo.

METHODOLOGY

Neonates (≥ 35 weeks) admitted in NICU in view of unconjugated hyperbilirubinemia for phototherapy as per UK-NICE guidelines will be enrolled after ruling out the exclusion criteria. Informed consent from parents will be taken prior to enrollment. The participants will be randomized in to three groups. They will receive either placebo or oral zinc @ 5 mg/day or 10mg/day once a day for 2 days. Each eligible neonate will be enrolled once into the study. Before starting phototherapy zinc levels will be sent and Neonates will be started on phototherapy with minimum 30µW/cm2/nm radiation intensity with age appropriate feed volume. Repeat serum bilirubin will be sent at 12, 24, 48hrs after starting of phototherapy and serum zinc level at 48 hrs of starting phototherapy.

The primary outcome will be measured by comparing decrease in unconjugated serum bilirubin in both zinc with 5mg and 10 mg oral group along with placebo group.

The secondary outcomes will be measured by comparing the duration of phototherapy, hospital stay, adverse events of the zinc and zinc levels pre and post phototherapy in intervention and placebo groups.

 P- Neonates (GA ≥ 35 weeks) admitted in NICU for phototherapy

I- Oral zinc sulphate supplementation (5mg or 10 mg/day) during phototherapy

C- Placebo during phototherapy

O- Total serum bilirubin at 12, 24,48hrs and adverse effect

T- Till NICU discharge

 Data inclusion:

All neonates who meet the inclusion criteria will be enrolled and demographic profile will be added in a excel sheet. A case Performa including information about day of jaundice, duration of phototherapy, and occurrence of side effects like vomiting, skin rash and diarrhea will be collected. Laboratory parameters like pre and post phototherapy  serum zinc level, complete blood count, blood group of mother and baby, glucose-6-phosphate dehydrogenase level (G6PD), thyroid function test (FT4 & TSH) and serum total, direct and indirect bilirubin will be recorded.

Statistical analysis:

The average values of continuous variables will be expressed as mean (SD) for normal distributed data; median (Q1, Q3) for skewness of data. Categorical variable will be expressed as frequency (%). The comparison of continuous variable between zinc (5mg/10mg) and placebo groups using independent samples t-test; chi-square and oblique fissure exact test will be used for comparison of categorical variable. P value of less than 0.05 to be considered as statistically significant. The data will be analyzed by using stat 1.5 software.

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