Supplementation With Lactoferrin in Preterm Newborns
Condition: Prematurity; Low Birth Weight
MeSH terms: Birth Weight
Study type: Interventional
Phase: Phase 4

Summary: 
      The main objective of the study is to evaluate the antioxidant effect of lactoferrin and its
      ability to reduce free radicals related diseases in the newborn. This evaluation will be done
      through the assessment of neuro-developmental follow-up.

      The secondary objective is to identify a panel of markers for assessing oxidative stress and
      for a correlation with the lactoferrin antioxidant effect.
    

Detailed description: 
      The study arises from the need to structure care to identify a product natural with
      antioxidant propriety that may reduce the extent of damage in perinatal neurological
      disorders related to oxidative stress by limiting the pain for infants and families and
      simultaneously reducing the cost to the SSN arising from standard pharmacological therapy and
      rehabilitation in the short and medium term. The research results will remain available to
      the scientific community and will not be used for profit or commercial. The iron (Fe) is the
      most abundant transition metal1 in the body and an essential element for growth and welfare
      of almost all life2 where he played a key role in many biochemical processes3. It is
      essential as cofactor in many enzymatic reactions and as catalyst in the processes of
      electron transport, yet is potentially toxic and rarely available. In the presence of oxygen
      Fe causes harmful action on the cell since it enhances the production by non-enzymatic
      reactive oxygen species. The hydroxyl radical in particular, can damage various cellular
      components such as DNA, proteins and membrane lipids. All bodies have therefore developed
      strategies that allow them to retain Fe was acquired in a soluble, nontoxic and in a form
      readily available. The Fe excess, also caused by weak bonds that the metal has with
      nonspecific and specific plasma proteins may carry out its negative effects by generating
      free radicals through the reactions of Fenton and Heber-Weiss4. Physiological requirements of
      Fe is higher during periods of rapid growth and differentiation, such as perinatal and
      nervous system that develops rapidly in late fetal life and early neonatal period, appears to
      be particularly sensitive to modulations of Fe contents5 In the newborn the inability to
      regulate, as necessary, the uptake of Fe by the immature gut may be the reason for failure
      and / or excess metal. Both situations may have adverse effects on neurological development
      of infants and in case of failure becomes irreversible even6-8 because any supplementation
      does not improve autcome9-11. In both cases the events that occur in early childhood have
      adverse effects on neuronal function in adults. The mechanism by which iron deficiency
      affects brain development is completely unknown but we know that can range up to a general
      lack metabolic errors of myelination and synaptogenesis and changes in specific funcions12 .
      It was also suggested that the adverse clinical outcomes in premature infants receiving blood
      transfusions and / or colonization13 may be related to oxidative damage14-17 <br>The main
      source of food for newborns is breast milk or formula. Breast milk contains heme Fe
      consequently the non-heme Fe, which is bound to milk proteins and other substances with lower
      molecular weight, is the main source of Fe in the diet of infants. The child is able to
      regulate the absorption of iron from the gut, in response to supplementation, only near the
      first year of life,18 so the inability of infants to regulate the intestinal absorption
      predisposes them to a deficiency when the Fe in the diet is insufficient, or an overload,
      when levels in the diet are high. It was also suggested that the enrichment of Fe in young
      children may lead to an increase in its plasma concentration and the formation of nonspecific
      compounds (nonspecific binding to proteins with low affinity bonds) that give rise to the
      so-called free Fe (NPBI) which originate from reactive oxygen species. Some authors have
      demonstrated increased oxidative stress in infants of very low birth weight who were
      subjected to a large oral iron supplementation, especially if breastfed seno.19-21 Although
      gestational age and some clinical treatments such as transfusions and ventilation considered
      because of an increased risk of oxidative damage Fe-indotto.22 Since the status of Fe in
      breast-fed term infants is usually satisfactory, at least until the sixth month, and an
      important part of Fe in human milk is bound to lactoferrin, has been previously suggested
      that the effect protective of human milk is related to the presence of this protein fixing
      most of the Fe and regulates its absorption. The lactoferrin is an iron-binding protein,
      naturally found in high concentrations in breast milk and in low concentrations in other
      fluids esocrini23. For the size and structure of lactoferrin is closely linked to another
      group of Fe-related protein, the transferrin and is considered by many as a member of this
      family. Lactoferrin binds iron with high affinity binding and its structure is unusually
      resistant to proteolytic degradation. Besides regulating the absorption of iron during
      inflammatory processes and infettivi24 performs several physiological functions including
      antibacterial, antifungal, antivirale25, antiparassitary26, antitumoral27,
      immunomodulator28-29. This ability antibacterial and antiviral properties, may explain the
      low prevalence and shorter duration of infection in breast-fed infants. In human milk
      lactoferrin plays an antioxidant sequestering free ions of Fe30 and thus preventing lipid
      peroxidation and subsequent milk oxidation31. Some AA.32 have shown this property in vitro
      using salts and Fe ions in the presence of a biological agent such as reducing ascorbato33. A
      recent study has also demonstrated its antioxidant effect in blood34. Again lactoferrin is
      able to bind free Fe, from binding studies, avoiding be sure to trigger a series of chain
      reactions that produce free radicals and thus reduces the damage induced by oxidative stress.
      This explains why breastfed children have significantly higher total antioxidant capacity and
      significantly lower index of oxidative stress. A recent study on infants supplied with
      formula supplemented with lactoferrin showed that presence of this protein helps the
      absorption of Fe in the small gut. The same study suggests that its activity could stimulate
      the proliferation and differentiation of mucosal cells in the gut35, thus increasing the
      surface and in turn increase the absorption of nutrients. Studies in pregnancy women 36
      suggests that lactoferrin may have an anti-inflammatory effect, while also improving the Fe
      status of women.
    

Intervention name(s): Lactoferrin; Lactoferrin
Intervention type(s): Drug; Drug
Intervention description(s): Experimental group: newborns (group A) will receive a daily dose of 100 mg of lactoferrin (Dicorfam® Elleffe 1''% 2C supplement containing lactoferrin) + standard therapy.
Control group: newborns (group B) will receive only standard therapy and they will be used as controls.; Experimental group: 650 newborns (group A) will receive a daily dose of 100 mg of lactoferrin (Dicorfam® Elleffe 1''% 2C supplement containing lactoferrin) + standard therapy.Control group: 650 newborns (group B) will receive only standard therapy and they will be used as controls.
Intervention MeSH terms: Lactoferrin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment