Skin and Serum Carotenoids in Preterm Infants Fed on a Formula Supplemented With Carotenoids

This study has been completed.
Sponsor:
Collaborator:
Abbott
Information provided by:
University of Utah
ClinicalTrials.gov Identifier:
NCT00872664
First received: March 30, 2009
Last updated: December 3, 2013
Last verified: December 2013
  Purpose

The primary objectives of this study are to compare the serum and skin concentrations of beta-carotene, lutein, and lycopene in preterm infants fed preterm formulas with mixed carotenoids to serum concentrations in preterm infants fed preterm formulas with no added carotenoids and to human milk fed infants.

The secondary objective of this study is to evaluate the effects of dietary carotenoids on the developing eye. Stages and zones of retinopathy of prematurity (ROP), retinal function, and retinal characteristics will also be examined.


Condition Intervention
Retinopathy of Prematurity
Dietary Supplement: carotenoids

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: Skin and Serum Carotenoids in Preterm Infants Fed on a Formula Supplemented With Carotenoids

Resource links provided by NLM:


Further study details as provided by University of Utah:

Primary Outcome Measures:
  • The primary objective is to compare the serum and skin levels of carotenoids in preterm infants fed formulas with mixed carotenoids to serum and skin levels in preterm infants fed formulas/human milk with no added carotenoids. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The secondary objective of this study is to evaluate the effects of dietary carotenoids on the developing eye. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment: 36
Study Start Date: September 2009
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: formula with added carotenoids
Both arms are double-blinded. Infant will be assigned to receive preterm formula with added carotenoids. If infant is receiving human milk then the study formula will only be used as a supplement.
Dietary Supplement: carotenoids
beta-carotene, lycopene, lutein
Active Comparator: formula without added carotenoids
Both arms are double-blinded. This arm will use preterm formula as it is currently available, which is without any carotenoids. If the infant is receiving human milk, then the formula will be used as a supplement as needed.
Dietary Supplement: carotenoids
beta-carotene, lycopene, lutein

Detailed Description:

Infants that are born prior to 37 weeks gestation often face complications resulting from their prematurity. Preterm infants are susceptible to morbidities that are not common in healthy term infants. Underdeveloped organs such as the lungs, eye, intestine, and brain can reveal conditions unique to prematurity: chronic lung disease, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), necrotizing enterocolitis, intraventricular hemorrhage (IVH), etc. Infants in the Newborn Intensive Care Unit (NICU) have increased inflammation and oxidative stress in association with common diseases of prematurity and as well as the treatments used to combat their illnesses (Gitto et al 2004; Ochoa et al 2003; Saugstad 2003).

According to the National Eye Institute (U.S. National Institutes of Health), retinopathy of prematurity affects approximately 50% of preterm infants that are born weighing 1250 g or less. While 90% of infants with retinopathy of prematurity (ROP) experience the milder form of the disease, which requires little or no medical treatment, severe ROP can lead to serious visual impairments or even blindness. This condition is of particular interest since Hylander et al. (Hylander et al 2001) have reported that human milk feeding of preterm infants (<1500 g birth weight) has been associated with a lower incidence of ROP and this association was proposed to be driven by the antioxidant content of human milk. Human milk provides a variety of antioxidants to the breastfed infant, including the carotenoids lutein, zeaxanthin, lycopene, and beta-carotene. As discussed earlier, lutein and zeaxanthin are concentrated to the eye and are thought to provide protection against both light-induced and metabolic oxidative damage.

The retina and retinal vasculature are the last eye structures to develop in the human fetus/neonate. Eyes of children with a history of ROP are reported to have retinal thinning with diffuse hypopigmentation, mild linearization, or mild tortuosity of the major vessel branch, mottled pigmentation of the macula, and other peripheral retinal anomalies (Minicucci et al 1999). The lack of pigmentation in the retinal structure might be explained by the deficit of lutein acquired by the fetus (by placental transfer during late gestation) or by the neonate through the diet (by preterm infant formulas devoid of these carotenoids). Preterm infants are at a nutritional disadvantage at birth as they have been deprived of the period of maximal transfer of nutrients during the last few weeks of pregnancy. Blood levels of beta-carotene have been associated with gestational age (Ostrea et al 1986) and cord blood levels of beta-carotene (Herrera et al 2004; Kiely et al 1999; Yeum et al 1998), lutein (Kiely et al 1999), and lycopene (Herrera et al 2004; Kiely et al 1999) were reported to be significantly lower than maternal levels. Stores of fat-soluble antioxidant vitamins also could be compromised due to the minimal fat deposition in the preterm infant.

It is therefore reasonable to suggest that providing preterm infants with a milk-based ready-to-feed (RTF) preterm infant formula with DHA and ARA supplemented with carotenoids, which are found in human milk, would result in serum carotenoid levels more like the breastfed infant. Further, increased dietary carotenoid intake by preterm infants might decrease the prevalence of morbidities that are associated with prematurity, such as ROP, bronchopulmonary dysplasia (BPD), and intraventricular hemorrhage (IVH).

  Eligibility

Ages Eligible for Study:   up to 21 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Birth weight 500-1500 g.
  • Less than 33 weeks gestational age (GA) at birth. Maternal dates will be used to estimate GA except in instances where a scan or the neonatologist's estimate differs by two weeks or more. In this instance, the scan or neonatologist's estimate of GA will be used. In the case where one neonatologist's estimate or scan confirms maternal dates and the other estimate does not confirm maternal dates, use the estimate of maternal dates.
  • Randomization within 96 hours of initiation of enteral feeding of >/= 60mL/kg/d of HM or formula
  • Formula fed infants' feeding consists of no more than 20% from human milk.
  • Enteral feeding initiated by 21 days of life (date of birth is Day 0 of life).
  • Parent/LAR agrees to allow infants to receive the assigned SSC Advance or NeoSure Advance formula in-hospital starting with the first enteral feed after randomization. If mother is providing breast milk, formula will only be given if there is not sufficient mother's milk.
  • Parent/LAR signed the informed consent.
  • SGA infants and infants with PDA are eligible to participate.
  • Singleton or twin births only. For twins to be eligible, both must meet inclusion criteria.

Exclusion Criteria:

  • Serious congenital abnormalities that may affect growth and development.
  • Grade III or IV IVH.
  • Maternal incapacity: including maternal cocaine or alcohol abuse during pregnancy or current, or if the mother or infant is currently receiving treatment consistent with HIV therapy.
  • History of major surgery (including surgery for NEC).
  • Asphyxia (hypoxia and ischemia) as evident by severe and permanent neurological damage.
  • Confirmed NEC (modified Bell's stage II or III) or positive blood cultures at the time of randomization
  • Infants who are enrolled in this clinical study should be excluded from participation in other concomitant studies. This exclusion criterion can be reviewed on a case-by-case basis. For example, infants will not normally be excluded if only demographic data are being collected or outcome measures on treatment modalities common to current clinical practice are being gathered.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00872664

Locations
United States, Utah
University of Utah Health Sciences Center
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
University of Utah
Abbott
Investigators
Principal Investigator: Gary M Chan, MD University of Utah
  More Information

No publications provided

Responsible Party: Dr. Gary Chan, University of Utah
ClinicalTrials.gov Identifier: NCT00872664     History of Changes
Other Study ID Numbers: 31886, ANUS 0805
Study First Received: March 30, 2009
Last Updated: December 3, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Utah:
ROP
anti-oxidants
carotenoids

Additional relevant MeSH terms:
Retinopathy of Prematurity
Retinal Diseases
Eye Diseases
Infant, Premature, Diseases
Infant, Newborn, Diseases
Carotenoids
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 01, 2014