Kan omega 3-fettsyror förbättra syn och utveckling hos för tidigt födda barn? - en interventionsstudie.
This project is under revision
Kan omega 3-fettsyror förbättra syn och utveckling hos för tidigt födda barn? - en interventionsstudie.
Project number : 100981
Created by: Ann Hellström, 2012-03-06
Last revised by: Ann Hellström, 2017-04-07
Project created in: FoU i Västra Götalandsregionen

Ongoing revisionOngoing revision

1. Översiktlig projektbeskrivning

Engelsk titel

A Randomised Intervention, Single-Center Study to Determine the Role of Fatty Acids in Serum in preventing Retinopathy of Prematurity

Populärvetenskaplig sammanfattning av projektet

We hypothesize that when preterm children are deprived of their natural environment they lose important factors normally found in utero, such as proteins, essential fatty acids, growth factors and cytokines. Preterm birth is one of the main causes of long term morbidity of different or-gan systems. It is strongly associated with adverse neurological and cognitive outcome, growth retardation, cardiovascular and pulmonary morbidity, retinopathy of prematurity (ROP) and other ocular and visual disturbances, reflecting exposure to an abnormal environment during the last trimester.
In the eye, normal retinal vascularisation takes place between the fourth gestational month and term. A physiological hypoxia created by increased demands of the maturating retina increases the levels of vascular endothelial growth factor (VEGF) which promotes retinal angiogenesis. In preterm babies, delayed growth of vessels and hyperoxia induced vessel loss may be fol-lowed by uncontrolled neovascularisation causing retinal detachment and blindness.
Available treatment with laser and cryo-therapy is based on destruction of the peripheral retina and only reduces blindness by 25%.
In recent animal and human studies we have found that postnatal lack of the growth factor In-sulin like growth factor I (IGF1) is associated with ROP and other prematurity related morbidi-ty [1]. In addition, a major binding protein (IGFBP3) protects against oxygen induced vessel loss [2]. These are only two of many substances lost by interruption of placental supply.
The development of the central nervous system (including the retina) which consists of 60% fat is highly dependent on fatty acids for proper development especially during the third trimester when growth is intense. The role of lipids in this process in the regulation of angiogenesis is largely unknown. Human breast milk (HM) contains long chain polyunsaturated fatty acids (LCPUFAs), such as omega 3 (docosahexaeonic acid, DHA) and omega 6 (arachidonic acid, AA), which are the major LCFPUFA components in membranes of the brain and retina, and which are absent from many infant formulas. Breast-fed infants have higher levels of DHA than formula-fed infants and are reported to have better cognitive development [3] and visual acuity, although some studies found no difference between the two groups [4]. In a recent re-view article it was concluded that preterm infants have a high need for DHA and AA to allow rapid brain and body growth. The content of AA is fairly constant in HM averaging about 0.45% of total FA while DHA levels vary with mothers´ diet (0.1-3.8%). A AA to DHA ratio of approximately 1.5 with a DHA content of 0.4% has been recommended for preterm in-fants[4].
In rats, DHA content in the rod outer segment increases rapidly postnatally from 30 to 70% of total FA [5]. A precursor of DHA is found in the retinal vascular endothelium [6].
In aa ROP mice model, we found that increasing the omega-3 PUFA levels by dietary or genet-ic means decreased the avascular retinal area by increasing vessel re-growth after injury, thereby reducing the hypoxic stimulus for neovascularisation. Increased levels of omega-3 protected against pathological angiogenesis and the omega-3 derived mediators neuroprotectinD1, re-solvinD1 and resolvinE1 also protected against neovascularisation. This protection was to a large part mediated through suppression of tumour necrosis factor α (TNFα) which was found in microglia adjacent to retinal vessels [7].
We now want to study whether supplementation of Omega-3 also protects against ROP in hu-mans.
Primary objectives

1) To determine how fatty acid (FA) levels in premature infants (born with a gestational age below 28 weeks) are affected by supplementation of “physiologic levels of long chain polyunsaturated fatty acids (LCPUFA) i.e. Omega-3 and 6.

2) To determine whether these FA levels protect against development of retinopathy of prematurity (ROP).

Secondary objectives

1)To determine whether these FA levels normalize growth (length, weight, head cir-cumference) and/or

2) To determine whether these FA levels reduce the risk of lung, brain and gut morbidi-ty

STUDY DESIGN

The study is a Randomised Intervention, Single-Center Study to Determine the Role of Fatty Acids in Serum and Breast Milk in preventing Retinopathy of Prematurity
Subjects who meet all inclusion and none of the exclusion criteria will be enrolled into the study. Upon entry into the study, subjects will be randomized and given a unique subject number.
A randomised intervention study of 100+100 (number based on power analysis regard-ing up to date ROP frequency, see 5.1) infants without major malformations born with a gestational age less than 28 weeks + 6 days will be performed.
Randomization of the patients to either
1)Conventional fatty acid supplementation regime with Clinoleic (with Vitalipid infant and Soluvit supplementation) to the preterm infant
Or
2)SMOFlipid (with Vitalipid infant and Soluvit supplementation), where the quo-tient of Omega 6:3 is 2.5:1 in order to mimic the physiologic relation of FAs in cord blood from birth, to the preterm infant.

Thus there is one group of infants (n=100) that will receive Omega-3 in the fatty acid supplementation.
The time on parenteral nutrition and the amount of fatty acids given will be according to clinical routines.
The randomization of the patients will be performed by the controller of the study Ran-domization will be in blocks with 20 children in each block.

Typ av projekt

Forskningsprojekt

MeSH-termer för att beskriva typ av studier

checked Longitudinella studier (Longitudinal Studies)
checked Prospektiva studier (Prospective Studies)
checked Klinisk prövning (Clinical Trial)
checked Randomiserad klinisk prövning (Randomized Controlled Trial)


(Only selected options are displayed. Click here to display all options)

MeSH-termer för att beskriva ämnesområdet

information Added MeSH terms
Fatty Acids, Omega-3
A group of fatty acids, often of marine origin, which have the first unsaturated bond in the third position from the omega carbon. These fatty acids are believed to reduce serum triglycerides, prevent insulin resistance, improve lipid profile, prolong bleeding times, reduce platelet counts, and decrease platelet adhesiveness.
Vision
The sensation of sight.
Infant, Premature
A human infant born before 37 weeks of GESTATION.
Child Development
The continuous sequential physiological and psychological maturing of an individual from birth up to but not including ADOLESCENCE.
Intervention Studies
Epidemiologic investigations designed to test a hypothesized cause-effect relation by modifying the supposed causal factor(s) in the study population.

Projektets delaktighet i utbildning

checked Avhandling
checked Annan utbildning


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Registrering i andra projektdatabaser

www.clinicaltrials.gov

2. Projektorganisation och finansiering

Arbetsplatser involverade i projektet

information Added workplaces
Landsting - Västra Götalandsregionen - Specialiserad vård - Sahlgrenska Universitetssjukhuset - Område 1 - Övrigt
Drottning Silvias barn och ungdomssjukhus, ögonmottagning

3. Processen och projektets redovisning

Hur långt har projektet framskridit?

Rekrytering/datainsamling inte påbörjad

Projektstart (när planeringen påbörjas och börjar dokumenteras skriftligt)

2009-01-07

Datum då projektet är slutrapporterat

2014-12-31

Länk till webbplats / webbsida

www.rop.gu.se
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Kan omega 3-fettsyror förbättra syn och utveckling hos för tidigt födda barn? - en interventionsstudie., from FoU i Sverige
http://www.researchweb.org/is/en/sverige/project/100981