Vitamin A and Very Low Birthweight Babies (VitAL)
Condition: Preterm Birth; Retinopathy of Prematurity
MeSH terms: Retinopathy of Prematurity; Premature Birth; Birth Weight
Study type: Interventional
Phase: Phase 4

Summary: 
      Vitamin A is important for the development of healthy eyes and lungs. Very low birth weight
      premature babies have low body stores of vitamin A and are prone to diseases of the eye and
      lungs. Previous work has shown that intramuscular (IM) vitamin A reduces the number of babies
      who require prolonged oxygen therapy, and may also reduce the number of babies affected by
      retinopathy of prematurity (ROP)). There is also some evidence that the conjunctiva shows
      signs of deficiency of vitamin A in premature infants, particularly those who develop ROP.
      Our own work here in Glasgow suggests that, compared to babies born at full term, premature
      babies' eyes are less sensitive to light and we believe that this may reflect shortage of
      vitamin A in the eye. This study will examine the effects upon the eye of giving extra
      intramuscular vitamin A to very low birth weight, premature infants. We will also measure
      blood levels of vitamin A and calculate liver stores of this nutrient.
    

Detailed description: 
      Eligible infant will be those infants born at < 32 completed weeks gestation and/or weighing
      < 1501 grams birth weight who have been admitted to either Princess Royal Maternity or Queen
      Mother's Hospital within the first 24 hours of life. If informed, written consent is obtained
      within 48-72 hours of birth, the infant will be randomised into either control or
      intervention group.

      The intervention group will receive IM vitamin A (Aquasol A)10,000IU three times weekly;
      control infants will receive mock injections. Injections will be continued for 4 weeks
      (maximum 12 injections). If enteral feeds are tolerated (defined as more than 75% of
      predicted intake via the enteral route)after the 14th day, oral vitamin A (as part of a
      multivitamin preparation) will be commenced and IM vitamin A discontinued. The dose of oral
      vitamin A will be 5000IU daily (= 0.6ml Dalivit), continued through discharge from the
      neonatal unit until the first birthday. The same oral vitamin supplement will be given to all
      VLBW babies, whether or not enrolled in this study. For infants receiving parenteral
      nutrition, Vitlipid N infant (4ml/kg/day) will be commenced on day 2, or at the discretion of
      the attending neonatologist. This will be given in addition to IM vitamin A.

      The study design is partially blinded whereby control infants will have mock injections (as
      described by Tyson et al.), rather than placebo injections. Infants randomised to placebo
      will simply have a sticking plaster applied to a leg prior to the screens being withdrawn.
      The research nurse will therefore be blinded to the infant's randomisation.

      Blood samples will be collected from enrolled infants at birth (or immediately after
      randomisation), on day 7, day 28 and at 36 corrected weeks. Samples will be separated, frozen
      and plasma retinol subsequently analysed by high pressure liquid chromatography.

      The RDR test will be performed as close as practicable to 36 corrected weeks, and whenever
      possible in conjunction with routine blood sampling. The baby will be given oral vitamin A,
      2000IU/kg, and a second specimen of blood obtained 3 hours after administration of vitamin A.
      As well as measurement of plasma retinol concentration, red blood cells will be analysed for
      the DHA content of the cell membrane.

      Retinal function will be assessed using the electroretinogram (ERG), in conjunction with
      routine ROP screening and as close as possible to 36 corrected weeks. The ERG
      luminance-response function will be recorded using different filters and background lighting
      to distinguish rod and cone responses. Conjunctival impression cytology (CIC) will be
      performed coincident with the ERG by taking a single sample from the bulbar conjunctiva,
      using a Millicell® filter.

      All infants will be examined weekly for signs of vitamin A toxicity, including mucocutaneous
      lesions, bone and joint abnormalities and fullness of the anterior fontanelle. Weekly blood
      tests during the period of IM injections will include full blood count and liver function.
    

Intervention name(s): Aquasol A; aquasol A; sham injection
Intervention type(s): Drug; Drug; Other
Intervention description(s): IM Aquasol A 10,000IU three times weekly; 10,000 IU three times weeks, by intramuscular injection; sham injection
Other intervention name(s): vitamin A; vitamin A
Intervention MeSH terms: Vitamins; Vitamin A; Retinol palmitate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: preterm; nutrition; vitamin A; electroretinogram; conjunctiva; vitamin A status; conjunctival health