The Effect of Zinc, β-carotene, and Vitamin D3 in Preterm Delivery Through Placental MyD88, TRIF, NFkB, and IL-1β

Study Overview
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Brief Summary
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This study is a controlled trial which compares the effect of zinc, beta-carotene, and Vitamin D3 supplementation in pregnant women which has preterm birth. The measured outcome is zinc, vitamin A, and 25(OH)D level in serum and placenta, MyD88, TRIF, NFκB, and IL-1β levels in placenta.

Detailed Description
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The research will be held in Cipto Mangunkusumo General and Budi Kemuliaan Hospital. Each participant of each group will be given the medication of preterm birth hospital protocol, which includes nifedipine 4x10 mg as tocolytic agent, dexamethasone 2x6 mg intravenous for 2 days which aims to support lung maturation, and antibiotic. Then, the blood sample is obtained for zinc, vitamin A and 25(OH)D levels examination. Subjects will be divided into 2 groups which are group whose given the oral zinc 50 mg/day, oral beta-carotene 25,000 IU and oral vitamin D3 50,000 IU/week supplementation, and group who is not given the intervention. Each participant will be observed until delivery. After delivery, level of zinc, vitamin A, and 25(OH)D in serum and placenta will be measured, as well as level of MyD88, TRIF, NFκB, and IL-1β in placenta.

Official Title
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The Effect of Zinc, Beta-carotene, and Vitamin D3 Supplementation as Pro-inflammation Mediated Regulator in Preterm Delivery Through Placental Protein Adaptor MyD88 and TRIF, Transcription Factor NFkB, and Pro-inflammatory Cytokine IL-1β

Conditions
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PreTerm Birth

Intervention / Treatment
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* Drug: Zinc
* Drug: Nifedipine
* Drug: Beta Carotene
* Drug: Vitamin D3
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women who has preterm birth in 26-36 weeks gestational age Exclusion Criteria: Multiple pregnancy Drug allergy Intra Uterine Growth Retardation (IUGR) is detected Congenital malformation in fetus was found Preterm Premature Rupture of Membrane (PPROM) Maternal complication such as gestational hypertension, preeclampsia, gestational diabetes mellitus, heart disease, infection, and autoimmune disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Intervention<br>Nifedipin 4x10 mg oral Dexamethasone 2x6 mg iv for 2 days Zinc 50 mg/day Beta-carotene 25,000 IU Vitamin D3 50,000 IU/weekly | Drug: Zinc<br>* included in intervention arm<br>* Other names: Zinc Picolinate 50 mg;Drug: Nifedipine<br>* included in intervention and control arm<br>* Other names: Nifedipine 10 mg;Drug: Beta Carotene<br>* included in intervention arm<br>* Other names: Beta carotene 25,000 IU;Drug: Vitamin D3<br>* included in intervention arm<br>* Other names: Cholecalciferol 50,000 IU;Drug: Dexamethasone<br>* included in intervention and control arm<br>* Other names: Dexamethasone 6 mg;|
| Active Comparator: Control<br>Nifedipin 4x10 mg Dexamethasone 2x6 mg iv for 2 days | Drug: Nifedipine<br>* included in intervention and control arm<br>* Other names: Nifedipine 10 mg;Drug: Dexamethasone<br>* included in intervention and control arm<br>* Other names: Dexamethasone 6 mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| placenta MyD88 | Placenta MyD88 will be measured by immunochemistry. The level will be compared between intervention and control group (percentage) | 1 year | 
| placenta TRIF | Placenta TRIF will be measured by immunochemistry. The level will be compared between intervention and control group (percentage) | 1 year | 
| Placenta NFkB | Placenta NFkB will be measured by immunochemistry. The level will be compared between intervention and control group (percentage) | 1 year | 
| Placenta 25(OH)D | Placenta 25(OH)D will be measured by LC-MS. The level will be compared between intervention and control group (ng/mL) | 1 year | 
| Placenta vitamin A | Placenta vitamin A will be measured by LC-MS. The level will be compared between intervention and control group (ng/mL) | 1 year | 
| Placenta zinc | Placenta zinc will be measured by ICP-MS. The level will be compared between intervention and control group (ug/L) | 1 year | 
| Placenta IL-1B | Placenta IL-1B will be measured by ELISA. The level will be compared between intervention and control group (pg/mL) | 1 year | 
| Serum zinc | Serum zinc will be measured by ICP-MS. The level will be compared between intervention and control group (ug/L) | 1 year | 
| Serum 25(OH)D | Serum 25(OH)D will be measured by LC-MS. The level will be compared between intervention and control group (ng/mL) | 1 year | 
| Serum vitamin A | Serum vitamin A will be measured by LC-MS. The level will be compared between intervention and control group (ng/mL) | 1 year |