A Fatty Acids Study in Preventing Retinopathy of Prematurity
Condition: Retinopathy of Prematurity
MeSH terms: Retinal Diseases; Retinopathy of Prematurity; Premature Birth
Study type: Interventional
Phase: Phase 3

Summary: 
      Most fatty acids, important for development and especially the Omega-3 fatty acids for the
      brain development are transferred in the third trimester with means that in the premature
      infant this transport via the placenta is interrupted and the infant is dependent on the
      concentrations in breast milk which vary depending on the mother's diet and her stores. It
      has even been suggested that low Omega-3 would be a cause of premature delivery. Many
      countries have much higher levels of Omega-3 fatty acids in breast milk than found in Sweden
      and breast milk substitutions are generally now supplemented with the Long Chained Poly
      Unsaturated Fatty Acids (LCPUFA). Therefore the supplementation to be given can not be seen
      to give any risks for the infant. On the contrary, several studies have shown that mother who
      eat equal to or less than twice fish a week during pregnancy give birth to infants with
      impaired development.

      Low Omega-3 levels in premature infants between gestational ages of 23 and 40 weeks can be
      one reason for Retinopathy of Prematurity (ROP) development. Restoration of Omega-3,
      Dokosahexaenacid (DHA) and Eikosapentaenacid (EPA) to normal in utero levels may prevent ROP
      by allowing normal vessel growth and survival. An increase of Omega-3 levels bringing levels
      to within physiological range may prevent development of ROP.
    

Detailed description: 
      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 45+45 infants without major malformations born with a
      gestational age less than 28 weeks + 0 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, (soybean oil, medium chain triglycerides, olive oil and fish oil),(with
           Vitalipid infant and Soluvit supplementation), where the quotient of Omega 6:3 is 2.5:1
           in order to mimic the physiologic relation of fatty acids in cord blood from birth, to
           the preterm infant.

      Thus there is one group of infants (n=45) 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.
      Randomization will be in blocks with 10 children in each block.

      Data collection

      After the investigators have received informed consent from the parents/guardians, blood
      samples 0.2 ml from the child will be taken according to present clinical practice at if
      possible from cord (2ml) and at days 0, 7, 14, 28 and in postmenstrual weeks 32, 36 and 40.
      Blood samples from the mothers for Fatty Acids analyses will be taken after birth, day 7 and
      at gestational weeks 36 and 40. At the same time (except from day 1), breast milk samples are
      taken. Length in cm, weight in gram and head circumference in cm are measured weekly.

      Screening for ROP will be performed, at least once a week, according to clinical routines
      using a specific protocol.

      The investigators intend to analyze the content of phospholipids which can be done on small
      amounts of blood, is relatively insensitive to short term fluctuations in intake and mirror
      the composition of many membranes in the body. The analyses will be made using gas-liquid
      chromatography. The method has a coefficient of variability of 1-3% for the Fatty Acids
      concerned.
    

Intervention name(s): SMOFlipid; Clinoleic
Intervention type(s): Drug; Drug
Intervention description(s): Parenteral fatty acid supplementation to preterm infants in preventing retinopathy of prematurity; Parenteral fatty acid supplementation to preterm infants in preventing retinopathy of prematurity
Intervention MeSH terms: SMOFlipid
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Retinopathy of Prematurity; Preterm; Fatty acids