Exclusive Human-milk in Preterm NEOnates and Early VASCular Aging Risk Factors (NEOVASC)

Study Overview
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Brief Summary
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Early vascular aging has its origins in fetal and neonatal life. The NEOVASC clinical trial aims to determine the effects of an exclusive human milk diet in extremely preterm infants on long-term cardiovascular health.

Detailed Description
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Early vascular aging has its origins in fetal and neonatal life. This early period of life plays an important role in the development of obesity, high blood pressure, abnormalities in lipid metabolism and non-insulin dependent diabetes. Increased cardiovascular risk in formerly preterm infants constitutes a health problem of steadily growing relevance. Emerging evidence suggests that human milk feeding has substantial benefits to the health of all infants, especially for those born prematurely. Unfortunately, human milk alone does not provide sufficient concentrations of nutrients, especially calcium, phosphorus, protein, and fat needed for these infants to grow satisfactorily. For that purpose, fortifiers are used to help increase the nutritional value of human milk. The NEOVASC study is a multicentric, prospective, randomized, controlled, open and parallel group clinical trial. A total of 200 extremely preterm infants and 100 term infants are recruited for the test and control group, respectively. Infants in the test group (i.e., premature neonates) are randomized to either: An exclusive human milk diet which contains mother's milk or pasteurized donor human milk and a human milk fortifier until 36 weeks of gestation; OR Human milk (as long as available) and a human milk fortifier (as long as human milk is available) until a maximum of 32 weeks of gestation and thereafter human milk with a bovine-based fortifier or preterm formula. After 36 weeks of gestation, human milk with a bovine-based fortifier or preterm formula is used in both groups. As a control group, term-born age-matched controls are included. Participants within this control group are not enrolled at the time of birth but instead recruited in various kindergartens at the age of five. Therefore, data from birth is taken from the mother-child-booklet, which contains clinical records about the pregnancy, birth and early life of children born in Austria. The total study duration is scheduled for 96 months with a recruitment phase of 36 months. Follow-up visits are planned at one, two and five years of age for the test group. The purpose of the NEOVASC clinical trial is to characterize early life stressors by assessing the effects of a physiological (i.e., human milk-based) nutrition in extremely preterm infants during the vulnerable preterm period on the risk of metabolic and vascular complications in later life. Outcomes include predictors and intermediate components of cardiovascular disease.

Official Title
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Effects of an Exclusive Human-milk Diet in Preterm NEOnates on Early VASCular Aging Risk Factors (NEOVASC)

Conditions
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Prematurity, Vascular Aging

Intervention / Treatment
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* Dietary Supplement: Humavant


Participation Criteria
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Eligibility Criteria
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Preterm-born group: Inclusion Criteria: Extremely preterm infants with a birth weight of 500-1250g. Feeding is NPO or exclusive human milk prior to enrollment. Parent(s) willing to sign informed consent.- Exclusion Criteria: Infants with a birth weight <500g or >1250g Subjects diagnosed with inborn errors of metabolism such as galactosemia, phenylketonuria Subjects who have not been NPO or fed exclusive human milk diet prior to enrollment. Presence of major congenital malformation. Presence of intestinal perforation or Stage 2 Necrotizing enterocolitis prior to enrollment. Parent(s) not willing to sign informed consent. Unable to participate for any reason based on the decision of the study investigator (e.g. unlikely to survive the study period). Term-born group: Inclusion criteria Term-born children with an adequate birth weight Parent(s) willing to sign informed consent Exclusion criteria Subjects with acute or chronic illness Parent(s) not willing to sign informed consent

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The NEO-VASC study is a multicentric, prospective, randomized, controlled, open and parallel group clinical trial.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Randomized study product group<br>receiving study product (human milk fortifier Humavant) until a gestational age of 36 weeks | Dietary Supplement: Humavant<br>* Premature infants are randomized to either: An exclusive human milk diet which contains mother's milk or pasteurized donor human milk and the human milk fortifier until 36 weeks of gestation; OR Human milk (as long as available) and the human milk fortifier (as long as human milk is available) until a maximum of 32 weeks of gestation and thereafter human milk with a bovine-based fortifier or preterm formula. After 36 weeks of gestation, human milk with a bovine-based fortifier or preterm formula is used in both groups. As a control group, term-born age-matched controls are included.<br>|
| Active Comparator: Randomized control group<br>receiving study product until a gestational age of 32 weeks and reference product (bovine based fortifier or bovine formula) after 32 weeks of gestation | Dietary Supplement: Humavant<br>* Premature infants are randomized to either: An exclusive human milk diet which contains mother's milk or pasteurized donor human milk and the human milk fortifier until 36 weeks of gestation; OR Human milk (as long as available) and the human milk fortifier (as long as human milk is available) until a maximum of 32 weeks of gestation and thereafter human milk with a bovine-based fortifier or preterm formula. After 36 weeks of gestation, human milk with a bovine-based fortifier or preterm formula is used in both groups. As a control group, term-born age-matched controls are included.<br>|
| No Intervention: Term control group<br>Term-born controls as a reference group for outcome parameters | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting blood glucose | Primary outcome is the difference in fasting blood glucose at five years of age | First day of life up to five years | 
| Blood pressure | Primary outcome is the difference in blood pressure at five years of age | First day of life up to five years | 
| Distensibility of aorta | Primary outcome is the difference in the distensibility of the descending aorta using validated echocardiographic protocols at five years of age | First day of life up to five years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting blood glucose | Secondary outcome is fasting glucose at a corrected age of one and two years. | First day of life up to 24 months | 
| Blood pressure | Secondary outcome is blood pressure at a corrected age of one and two years. | First day of life up to 24 months | 
| BMI | Secondary outcome is BMI at five years of age, weight in kilograms and height in meters will be combined to report BMI in kg/m2 | First day of life up to five years | 
| Insulin sensitivity | Secondary outcome is insulin sensitivity at five years of age | First day of life up to five years | 
| Lipid profile | Secondary outcome is lipid profile at five years of age | First day of life up to five years |