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

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

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.

Study Overview

• Status: Completed
• Conditions: PreTerm Birth
• Intervention / Treatment: Drug: Zinc; Drug: Nifedipine; Drug: Beta Carotene; Drug: Vitamin D3; Drug: Dexamethasone

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Indonesia University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: December 19, 2016
• First Submitted That Met QC Criteria: December 23, 2016
• First Posted (Estimate): December 29, 2016

Study Record Updates

• Last Update Posted (Actual): November 21, 2017
• Last Update Submitted That Met QC Criteria: November 18, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Protective Agents; Trace Elements; Micronutrients; Membrane Transport Modulators; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Reproductive Control Agents; Calcium Channel Blockers; Antioxidants; Chelating Agents; Sequestering Agents; Tocolytic Agents; Iron Chelating Agents; Provitamins; Dexamethasone; Dexamethasone acetate; BB 1101; Vitamin D; Cholecalciferol; Nifedipine; Beta Carotene; Carotenoids; Zinc; Picolinic acid
• Other Study ID Numbers: 50/UN.2F1/ETIK/2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The research findings will be disseminated via publication of results, submission of information to public accessible databases, or meetings