Effects of Fat-soluble Vitamins Supplementation on Common Complications and Neural Development in Very Low Birth Weight Infants

• ClinicalTrials.gov Identifier: NCT03876704
• Recruitment Status: Recruiting
• First Posted: March 15, 2019
• Last Update Posted: March 15, 2019
• Sponsor: First Affiliated Hospital Xi'an Jiaotong University
• Collaborator: Xi'an Gaoxin Hospital
• Information provided by (Responsible Party): First Affiliated Hospital Xi'an Jiaotong University

Study Description

Brief Summary:

Vitamins A, D, and E play important roles in humans, such as vision function, immune function, bone metabolism, cell growth and differentiation and oxidation resistance. Deficiencies in these vitamins will result in a high prevalence of cardiovascular disease, infection, bone diseases, etc. Preterm infants, especially very low birth weight infants, are at risk of vitamin deficiency. Intravenous perfusion is the most common and widely used method to supply vitamins for the specific population in early life. However, the current dose of vitamin supplied by intravenous perfusion whether can meet the need of growth and development is not sure and the appropriate dose for preterm infants is still uncertain. The purpose of this study is to investigate whether current dose of fat-soluble vitamin supplementation is enough for very low birth weight infants, the safety of high dose of fat-soluble vitamin supplementation, and compare the differences of prevalence of common complications, such as bronchopulmonary dysplasia, patent ductus arteriosus, sepsis, anemia, and neural development between these two groups.

Condition or disease	Intervention/treatment	Phase
Vitamin A Deficiency; Vitamin D Deficiency; Vitamin E Deficiency; Very Low Birth Weight Infants; Bronchopulmonary Dysplasia; Anemia; Sepsis	Drug: High dose of fat-Soluble Vitamin; Drug: Conventional dose of fat-Soluble Vitamin	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effects of Fat-soluble Vitamins Supplementation in Early Life on Common Complications and Neural Development in Very Low Birth Weight Infants
• Actual Study Start Date: January 29, 2019
• Estimated Primary Completion Date: September 30, 2019
• Estimated Study Completion Date: December 31, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: High dose of fat-soluble vitamins; Fat-soluble vitamins is administered 0.5 piece/kg (equals to 1150 U/kg vitamin A，200 U/kg vitamin D, 3.2 U/kg vitamin E) intravenously every day until the baby achieve full enteral feeding (120 ml/kg), starting with the first dose within 24 hours after birth.	Drug: High dose of fat-Soluble Vitamin; Supplementation of 5 times current dose of fat-soluble vitamins by intravenous perfusion
Active Comparator: Conventional dose of fat-soluble vitamins; Fat-soluble vitamins is administered 0.1 piece/kg (equals to 230 U/kg vitamin A，40 U/kg vitamin D, 0.64 U/kg vitamin E) intravenously every day until the baby achieve full enteral feeding (120 ml/kg), starting with the first dose within 24 hours after birth.	Drug: Conventional dose of fat-Soluble Vitamin; Supplementation of the current dose of fat-soluble vitamins by intravenous perfusion

Outcome Measures

Primary Outcome Measures :

1. Vitamin levels [ Time Frame: within 72 hours after birth, 4~6 weeks old ]
   Change from baseline level of vitamin A, vitamin D, and vitamin E at 4~6 weeks

Secondary Outcome Measures :

1. Complications [ Time Frame: corrected age of 36 weeks ]
   The prevalence of bronchopulmonary dysplasia, patent ductus arteriosus, sepsis, anemia, intracranial hemorrhage, extrauterine growth retardation, etc.
2. Neural development [ Time Frame: corrected age of 40 weeks ]
   White matter disease of the preterm infant, was semiquantitatively assessed from MRI at term-equivalent age based on an established scoring method.
3. Gene polymorphism in vitamin deficiency preterm infants [ Time Frame: within 72 hours after birth, 4~6 weeks old ]
   Association of rs4588 polymorphism in vitamin D receptor gene and rs10766197 polymorphism in the cytochrome P450 family 2 subfamily R member 1 gene with baseline level of vitamin D and change in vitamin D level after 4~6 weeks' supplementation

Eligibility Criteria

• Ages Eligible for Study: up to 24 Hours (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• admitted to the neonatal intensive care unit (NICU) within 24 hours after birth
• gestational age younger than 34 weeks
• birth weight less than 1500 gram
• informed consent was obtained from the infants' parents or guardians

Exclusion Criteria:

• congenital malformation
• chromosomal disease, genetic metabolic diseases
• the infants or his/mother has abnormal thyroid function or parathyroid gland function
• neonatal necrotizing enterocolitis, diarrhea
• intracranial hemorrhage of 3 degrees or above
• pulmonary hemorrhage
• liver enzymes elevated by more than 2 times, cholestasis
• death or discharge against medical advice
• refuse to take part in the study

Contacts and Locations

Contacts

Contact: Shuang Liu; 008615201524806; liushuangpku@126.com

Locations

China, Shaanxi

First Affiliated Hospital of Xian JiaotongUniversity; Recruiting

Xi'an, Shaanxi, China, 710061

Contact: Xihui Zhou

Sponsors and Collaborators

First Affiliated Hospital Xi'an Jiaotong University

Xi'an Gaoxin Hospital

Investigators

• Study Director: Shuang Liu; First Affiliated Hospital of Xian JiaotongUniversity

More Information

Publications of Results:

Fares S, Sethom MM, Khouaja-Mokrani C, Jabnoun S, Feki M, Kaabachi N. VitaminA, E, and D deficiencies in tunisian very low birth weight neonates: prevalence and risk factors. Pediatr Neonatol. 2014 Jun;55(3):196-201. doi: 10.1016/j.pedneo.2013.09.006. Epub 2013 Nov 26.

Other Publications:

Kositamongkol S, Suthutvoravut U, Chongviriyaphan N, Feungpean B, Nuntnarumit P. Vitamin A and E status in very low birth weight infants. J Perinatol. 2011 Jul;31(7):471-6. doi: 10.1038/jp.2010.155. Epub 2011 Jan 13.

Mactier H, Mokaya MM, Farrell L, Edwards CA. Vitamin A provision for preterm infants: are we meeting current guidelines? Arch Dis Child Fetal Neonatal Ed. 2011 Jul;96(4):F286-9. doi: 10.1136/adc.2010.190017. Epub 2011 Jan 17.

Jilani T, Iqbal MP. Vitamin E deficiency in South Asian population and the therapeutic use of alpha-tocopherol (Vitamin E) for correction of anemia. Pak J Med Sci. 2018 Nov-Dec;34(6):1571-1575. doi: 10.12669/pjms.346.15880. Review.

Cho SY, Park HK, Lee HJ. Efficacy and safety of early supplementation with 800 IU of vitamin D in very preterm infants followed by underlying levels of vitamin D at birth. Ital J Pediatr. 2017 May 4;43(1):45. doi: 10.1186/s13052-017-0361-0.

• Responsible Party: First Affiliated Hospital Xi'an Jiaotong University
• ClinicalTrials.gov Identifier: NCT03876704
• Other Study ID Numbers: 2018MSZC-04
• First Posted: March 15, 2019
• Last Update Posted: March 15, 2019
• Last Verified: February 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Bronchopulmonary Dysplasia; Night Blindness; Vitamin D Deficiency; Vitamin A Deficiency; Vitamin E Deficiency; Body Weight; Birth Weight; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Vision Disorders; Eye Diseases; Vitamins; Micronutrients; Nutrients; Growth Substances; Physiological Effects of Drugs