The Effect of β-Carotene, Vitamin D3 and Zinc on Hyaline Membrane Disease and Feeding Intolerance in Premature Neonates

The Effect of Co-administered β-Carotene, Vitamin D3, Zinc and Antenatal Steroid Therapy on Hyaline Membrane Disease and Feeding Intolerance in Premature Neonates

Hyaline membrane disease, now commonly called respiratory distress syndrome (RDS), and feeding intolerance, which can lead to necrotizing enterocolitis (NEC), are two key morbidities found in premature neonates which resulted in high mortality rate in Indonesia. Cochrane meta-analysis proved that antenatal steroid therapy can reduce the morbidity and mortality rate of premature neonates. But there is still different outcomes and severity of disease in preterm newborn receiving the same dose of antenatal steroid therapy. This raises questions whether there are other factors influencing the development and maturity of lung and gut in preterm newborn, aside from steroid therapy. Vitamin A, D and zinc are already known for their function in fetal lung and gut development. To our best of knowledge, no study has evaluated the effect of these vitamins levels on HMD and feeding intolerance in premature neonates. Therefore, the aim of this study want to evaluate the effect of antenatal steroid therapy versus co-administered β-carotene, vitamin D3, zinc and antenatal steroid therapy on the presence and severity of HMD and feeding intolerance in premature neonates.

Study Overview

• Status: Unknown
• Conditions: Hyaline Membrane Disease; Necrotizing Enterocolitis of Newborn
• Intervention / Treatment: Dietary supplement: Beta carotene; Dietary supplement: Vitamin D3; Dietary supplement: Zinc; Drug: Dexamethasone

Detailed Description

This study is a randomized controlled trial and held in Cipto Mangunkusumo Hospital.

Pregnant women 28-34 weeks of gestational age, who fulfill the inclusion criteria, divide into two groups. Subjects from both groups receive the hospital protocol of preterm birth, 4 doses of 6 mg of dexamethasone, intravenous 12 hours apart to support lung maturation. Subjects in intervention group receive oral single-dose beta-carotene 25,000 IU, oral single-dose vitamin D3 50,000 IU and oral zinc 50 mg/day for 3 days. The maternal dan cord blood sample are obtained for zinc, vitamin A and 25(OH)D levels before and after intervention. After the premature neonates was born, observation will be done for maximum period of 4 weeks. The presence and severity of HMD and feeding intolerance or NEC will be recorded. Neonates showing any signs of HMD and/or abdominal distension will need to undergo additional chest/abdominal x-ray procedures.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• Indonesia
  • DKI Jakarta
    • Jakarta, DKI Jakarta, Indonesia, 12440
      • Recruiting
      • Cipto mangunkusumo general hospital
      • Contact: Yuyun Lisnawati, Consultant; Phone Number: +628161841987; Email: yulisna.er@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 45 years (ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Pregnant women who has preterm birth in 28-34 weeks gestational age

Exclusion Criteria:

• Multiple pregnancy
• Drug allergy
• Fetal congenital malformation
• Maternal gestational diabetes mellitus

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Intervention; beta carotene 25,000 IU; vitamin D3 50,000 IU; zinc 50 mg; dexamethasone 6 mg	Dietary supplement: Beta carotene; Beta carotene 25,000 IU; Dietary supplement: Vitamin D3; Vitamin D3 50,000 IU; Other Names: Cholecalciferol; Dietary supplement: Zinc; Zinc 50 mg; Other Names: Zinc picolinate; Drug: Dexamethasone; Dexamethasone 6 mg
ACTIVE_COMPARATOR: Control; dexamethasone 6 mg	Drug: Dexamethasone; Dexamethasone 6 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hyaline membrane disease	The presence and severity of RDS (HMD) will be noted, according to chest X-ray result	1,5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feeding Intolerance	The presence and severity of necrotican enterocolitis will be noted, according to abdominal x-ray result	1,5 years

Collaborators and Investigators

• Sponsor: Indonesia University
• Investigators: Study Chair: Yuyun Lisnawati, Persahabatan General Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2017
• Primary Completion (ANTICIPATED): December 1, 2018
• Study Completion (ANTICIPATED): June 1, 2019

Study Registration Dates

• First Submitted: December 3, 2017
• First Submitted That Met QC Criteria: December 3, 2017
• First Posted (ACTUAL): December 8, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 13, 2018
• Last Update Submitted That Met QC Criteria: August 9, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Gastrointestinal Diseases; Infant, Newborn, Diseases; Gastroenteritis; Intestinal Diseases; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Infant, Premature, Diseases; Respiratory Distress Syndrome, Newborn; Respiratory Distress Syndrome; Premature Birth; Enterocolitis; Enterocolitis, Necrotizing; Hyaline Membrane Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protective Agents; Trace Elements; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Antioxidants; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Provitamins; Dexamethasone; Vitamin D; Cholecalciferol; Beta Carotene; Carotenoids; Zinc; Picolinic acid
• Other Study ID Numbers: 190/2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The research findings will be disseminated via publication of results

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No