Correlation of CXCR4 Expression in Premature Infants With a Diagnosis of Autism at 24 Months
Condition: Autism Spectrum Disorder; Complication of Prematurity
MeSH terms: Premature Birth; Autistic Disorder; Autism Spectrum Disorder
Study type: Observational

Summary: 
      Preterm children are at increased risk for autism spectrum disorders, with an estimated rate
      of 10%. In the US, about 1 in 8 pregnancies ends with a premature birth. Therefore,
      individuals with ASD who were born prematurely form a substantial body of children diagnosed
      with ASD.

      Premature birth confers an insult to the newborn at a neurologically vulnerable stage.
      Prematurity associated changes in oxygen tension can be detrimental to developing organs, the
      brain being one of the most rapidly developing organs in the second half of the pregnancy.
      Changes in oxygen tension mediate activation of proteins that change the course of cell
      development.

      In this study, we plan to measure changes in the expression of 3 proteins that may be
      affected by changes in oxygen level at birth. We will study the interaction between the
      proteins' levels in the first few days after premature birth with a diagnosis of ASD at 2
      years of age. The proteins are:

        1. VEGF (Vascular Endothelial Growth Factor), a protein that takes part in creating new
           blood vessels during embryonic development.

        2. Hypoxia-inducible factor -1(HIF-1), a key protein that coordinates expression of
           different genes, many with developmentally critical functions.

        3. CXCR4, a cell surface protein that is activated by SDF-1. SDF- 1 is a molecule that
           regulates migration of cells to their target destination during embryonic life. CXCR4 is
           expressed in areas of the brain and on cells that are known to be associated with ASD.

      We hypothesis that changes in oxygen tension in premature babies initiates a cascade of
      events that lead to changes in cell mobility via abnormal CXCR4 expression. This change leads
      to abnormal neurodevelopment.

      The investigators' primary aim is to find if there is a correlation between postnatal levels
      of expression of HIF-1, CXCR4 and VEGF and a diagnosis of autism at age 24 months. The
      investigators' secondary aim is to find if there is a correlation between postnatal levels of
      expression of HIF-1, CXCR4 and VEGF and a language or neurocognitive delay.

      Methods:

        1. Premature babies will be recruited in the first day post delivery.

        2. Blood samples will be collected at 3 time points during their hospitalization, and the
           expression of HIF-1, CXCR4 and VEGF will be determined.

        3. Infants will undergo a complete developmental evaluation at 18-24 months of age .

        4. Postnatal levels of HIF, CXCR4 and VEGF will be plotted against the results of the
           developmental evaluation.
    


Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        neonatal intensive care units newborn ward
      
Biospecimen description: 
      blood samples. expression of proteins or RNA will be determined from the blood.
    
Keywords: ASD; autism; prematurity; oxygen-dependant gene activation; CXCR4; Language delay; Cognitive delay